Coating medical devices

ABSTRACT

Methods and systems for coating at least a portion of a medical device (e.g., a stent structure) include providing a plurality of coating particles (e.g., monodisperse coating particles) in a defined volume. For example, the particles may be provided using one or more nozzle structures, wherein each nozzle structure includes at least one opening terminating at a dispensing end. The plurality of coating particles may be provided in the defined volume by dispensing a plurality of microdroplets having an electrical charge associated therewith from the dispensing ends of the one or more nozzle structures through use of a nonuniform electrical field between the dispensing ends and the medical device. Electrical charge is concentrated on the particle as the microdroplet evaporates. With a plurality of coating particles provided in the defined volume, such particles can be moved towards at least one surface of the medical device to form a coating thereon (e.g., using an electric field and/or a thermophoretic effect).

CROSS REFERENCE TO RELATED APPLICATIONS

This is a continuation-in-part of U.S. patent application Ser. No.09/858,865 filed 16 May 2001 entitled “High Mass Throughput ParticleGeneration Using Multiple Nozzle Spraying,” incorporated herein byreference.

BACKGROUND OF THE INVENTION

The present invention relates to coating medical devices, and moreparticularly, the present invention relates to coating medical devicesusing processes such as electrospray, thermophoretic effect, etc.

It is often beneficial to coat medical devices so that the surfaces ofsuch devices have desired properties or provide desired effects. Forexample, it is useful to coat medical devices to provide for thelocalized delivery of therapeutic agents to target locations within thebody, such as to treat localized disease (e.g., heart disease) oroccluded body lumens. Local drug delivery may be achieved, for example,by coating balloon catheters, stents, and the like with therapeuticagent to be locally delivered. The coating of medical devices mayprovide for controlled release, which includes long-term or sustainedrelease, of a bioactive material.

Aside from facilitating localized drug delivery, medical devices arecoated with materials to provide beneficial surface properties. Forexample, medical devices are often coated with radiopaque materials toallow for fluoroscopic visualization during placement in the body. It isalso useful to coat certain devices to achieve enhanced biocompatibilityand to improve surface properties such as lubriciousness.

As indicated herein, it is often beneficial to coat stents, e.g., forthe controlled release of pharmacological agents, surface propertycontrol and effects, etc. Stents are implanted within vessels in aneffort to maintain the patency thereof by preventing collapse and/orimpeding restenosis. For example, implantation of a stent may beaccomplished by mounting the stent on the expandable portion of aballoon catheter, maneuvering the catheter through the vasculature so asto position the stent at the treatment site within the body lumen, andinflating the balloon to expand the stent so as to engage the lumenwall. The stent deforms in the expanded configuration allowing theballoon to be deflated and the catheter removed to complete theimplantation procedure. Further, for example, the use of self-expandingstents obviates the need for a balloon delivery device. Instead, aconstraining sheath that is initially fitted above the stent is simplyretracted once the stent is in position adjacent the treatment site.Stents and stent delivery catheters are well known in the art and thevarious configurations thereof makes it impossible to describe each andevery stent structure or related materials.

The success of a stent placement can be assessed by evaluating a numberof factors, such as thrombosis, neointimal hyperplasia, smooth musclecell migration, and proliferation following implantation of the stent,injury to the artery wall, overall loss of lumenal patency, stentdiameter in vivo, thickness of the stent, and leukocyte adhesion to thelumenal lining of stented arteries. The chief areas of concern are earlysubacute thrombosis and eventual restenosis of the blood vessel due tointimal hyperplasia.

Therapeutic pharmacological agents have been developed to address someof the concerns associated with the placement of the stent. It is oftendesirable to provide localized pharmacological treatment of the vesselat the site being supported by the stent. As it would be convenient toutilize the implanted stent for such purpose, the stent may serve bothas a support for a lumenal wall as well as a delivery vehicle for thepharmacological agent.

Conventionally, coatings have been applied to medical devices, includingstents, by processes such as dipping, spraying, vapor deposition, plasmapolymerization, as wells as electroplating and electrostatic deposition.Although many of these processes have been used to produce satisfactorycoatings, there are numerous potential drawbacks associated therewith.

For example, it is often difficult to achieve coatings of uniformthicknesses, both on the individual parts and on batches of parts. Also,many coating materials are otherwise difficult to use, such as thosethat are incompatible, insoluble, unsuspendable, or that are unstablecoating solutions.

Further, for example, many coating processes result in coatings that donot provide a uniform drug dose per medical device. Further, suchconventional methods have generally failed to provide a quick, easy, andinexpensive way of providing drugs onto a stent. For example,deficiencies of such conventional methods are, at least in part, relatedthe control of the coating process (e.g., the ability to control thecoating uniformity and thickness, the ability to control the size ofparticles used to coat the device, the control of the coating so as tocontrol the rate of the release of the drug upon implantation of thestent, etc.). Likewise, in many processes, the coating materials arefairly costly, and in many coating processes such coating materials arewasted due to the type of coating methods being used.

Therefore, the need for an effective method and system of coatingmedical devices exists (e.g., one that results in a uniform coating onthe medical device, such as a stent structure).

SUMMARY OF THE INVENTION

The methods and systems according to the present invention provide forthe coating of medical devices (e.g., stents, catheters, etc.). Thepresent invention is particularly beneficial for use in coating stentstructures.

A method of coating at least a portion of a medical device according tothe present invention includes providing a medical device in a definedvolume. The medical device includes at least one surface to be coated.The method further includes providing a plurality of monodispersecoating particles in the defined volume. The plurality of monodispersecoating particles have a nominal diameter of less than 10 micrometersand a geometrical standard deviation of less than 1.2. A plurality ofthe coating particles are moved towards the at least one surface of themedical device to form a coating thereon.

Another method of coating at least a portion of a medical deviceaccording to the present invention includes providing a medical devicein a defined volume (e.g., the medical device including at least onesurface to be coated) and providing one or more nozzle structures,wherein each nozzle structure includes at least one opening terminatingat a dispensing end. A plurality of coating particles are provided inthe defined volume by dispensing a plurality of microdroplets having anelectrical charge associated therewith from the dispensing ends of theone or more nozzle structures using a nonuniform electrical fieldcreated between the dispensing ends and the medical device. Each of themicrodroplets includes at least a particle and the electrical charge isconcentrated on the particle as the microdroplet evaporates. The methodfurther includes moving the plurality of coating particles towards themedical device to form a coating on the at least one surface of themedical device using the nonuniform electrical field created between thedispensing ends from which the plurality of coating particles isestablished and the medical device.

A method of coating a stent structure is also described herein. Themethod includes providing a stent structure in a defined volume along astent axis, wherein the stent structure includes at least an interiorsurface adjacent a defined interior volume and at least an exteriorsurface. At least a portion of the interior surface of the stentstructure adjacent the defined interior volume is coated using at leasta plurality of first coating particles (e.g., anti-coagulant particles)and at least a portion of the exterior surface of the stent structure iscoated using at least a plurality of second coating particles (e.g.,anti-inflammatory particles), wherein the plurality of first coatingparticles is different than the plurality of second coating particles.

The methods described above may also include one or more of thefollowing features: providing an electrical charge on the plurality ofmonodisperse coating particles; moving a plurality of monodispersecoating particles towards a medical device using an electrical field;providing a plurality of monodisperse coating particles by dispensing aspray of microdroplets having an electrical charge associated therewith,wherein each of the microdroplets includes a particle and wherein theelectrical charge is concentrated on the particle as the microdropletevaporates; an electrical charge of a microdroplet concentrated on theparticle that is greater than about 30 percent of the Rayleigh chargelimit for the microdroplet; providing a plurality of monodispersecoating particles by dispensing a spray of microdroplets having anelectrical charge associated therewith, wherein the electrical charge isconcentrated on the particle as the microdroplet evaporates and furtherwherein, prior to contact with the at least one surface of the medicaldevice, a residual particle volume occupied by the evaporatedmicrodroplet includes less than about 20 percent of a solvent componentof the microdroplet; creating an electrical field between an electrodeand the medical device after the monodisperse coating particles areprovided in the defined volume; providing a plurality of monodispersecoating particles using one or more nozzle structures, wherein eachnozzle structure includes at least one opening terminating at adispensing end thereof from which a plurality of monodisperse coatingparticles having an electrical charge applied thereto is dispensed;dispensing a plurality of monodisperse coating particles from each of aplurality of nozzle structures by creating a nonuniform electrical fieldbetween the dispensing ends of the nozzle structures from which aplurality of monodisperse coating particles are dispensed and a medicaldevice; moving a plurality of monodisperse coating particles towards atleast one surface of a medical device to form a coating thereon using anonuniform electrical field created between dispensing ends from whichthe plurality of monodisperse coating particles are dispensed and amedical device; providing a medical device that includes a structuredefining an interior volume, wherein the structure comprises at least aninterior surface adjacent the interior volume and at least an exteriorsurface that is not adjacent to the interior volume; providing at leastone nozzle structure having at least one opening at the dispensing endthereof located within the interior volume defined by a structure anddispensing a plurality of monodisperse coating particles from the atleast one nozzle structure with use of a nonuniform electrical fieldcreated between the dispensing end of the at least one nozzle and themedical device; providing at least one nozzle structure that includes acapillary tube comprised of a body portion and a tapered capillary tipat the dispensing end of the capillary tube; providing a medical devicein a fixed position within a defined volume during the coating process;and providing a medical device that is movable within a defined volumeduring the coating process.

The method may further include one or more of the additional followingfeatures: providing a stent structure defined along a stent axis,wherein the stent structure includes at least an interior surfaceadjacent a defined interior volume and at least an exterior surface thatis not adjacent to the defined interior volume; providing one or morenozzle structures, wherein each nozzle structure includes at least oneopening terminating at a dispensing end thereof from which a pluralityof monodisperse coating particles having an electrical charge appliedthereto is dispensed; adjusting the strength of a nonuniform electricalfield to prevent particles from reaching an interior surface of a stentstructure; dispensing a plurality of monodisperse coating particles fromat least one nozzle structure using a nonuniform electrical fieldcreated between a dispensing end thereof and a stent structure; moving aplurality of monodisperse coating particles towards at least one surfaceof a medical device using a thermophoretic effect; positioning a stentstructure such that the stent axis coincides with an axis of anelongated element located within the interior volume of the stentstructure and holding the elongated element at a lower temperature thanthe temperature in the defined volume adjacent the exterior surface ofthe stent structure such that thermophoretic effect moves the coatingparticles towards the at least one surface of the stent structure;rotating a stent structure about a stent axis during the coatingprocess; moving a stent structure linearly along a stent axis;controlling the amount of monodisperse coating particles provided into adefined volume; providing a plurality of coating particles that have anominal diameter of greater than about 1 nanometer and less than about100 nanometers, that include at least one biologically active ingredientor a coated biologically active ingredient, and/or that include at leastone of DNA or coated DNA; providing a plurality of coating particles ina defined volume have a nominal diameter of less than 10 micrometers anda geometrical standard deviation of less than 1.2; and providing one ormore nozzle structures that each include at least a first and secondopening terminating at the dispensing end of each nozzle structure(e.g., for dispensing coated particles, dispensing hard to sprayparticles, dispensing particles that define voids therewithin, etc.).

The methods described herein, preferably those used to coat stentstructures, may include one or more of the following features: providingan elongated cylindrical body member defining an interior volume thereofalong an axis, positioning the stent structure along the axis of theelongated cylindrical body member, and positioning a plurality of nozzlestructures radially about the axis of the elongated cylindrical bodymember and linearly along the elongated cylindrical body member in thedirection of the axis thereof; providing nozzle structures that eachinclude a capillary tube comprised of a body portion and a taperedcapillary tip at the dispensing end of the capillary tube; providingnozzles structures that each include a tapered portion used to define anopening, and wherein at least a part of each of the plurality of thenozzle structures extend from an integral conductive portion associatedwith the body member; providing a plurality of the nozzle structuresthat each include a solid post along a center axis extending through anopening at the dispensing end; providing one or more nozzle structuresthat may include an elongated radial opening in the body member and/oran elongated opening in the body member lying parallel to the axisthereof; positioning a stent structure such that the stent axiscoincides with an axis of an elongated element and using spacingelements to maintain a distance between the stent structure and theelongated element; positioning a stent structure such that the stentaxis coincides with an axis of an elongated element, wherein theelongated element is sized based on the defined interior volume of thestent structure such that a surface of the elongated element is indirect contact with the interior surface of the stent structure;removing an elongated element from the interior volume of the stentstructure after a plurality of coating particles are moved towards theexterior surface of the stent structure to form a coating thereon;providing a stent structure that includes an open framework includingstent material lying radially from the stent axis and a configuration ofopenings separating portions of the stent material; providing anelongated element sized to stretch the stent structure from a normalstate; removing an elongated element from an interior volume of a stentstructure after a plurality of coating particles are moved towards theexterior surface of the stent structure resulting in a sheath over theopen framework thereof including openings separating portions of stentmaterial; providing a conductive elongated element along the axis of thestent structure, wherein the stent structure and the conductiveelongated element are spaced a distance apart, and creating an electricfield between the conductive elongated element and the stent structurethat is opposite a nonuniform electric field created between dispensingends of nozzle structures and the stent structure; providing anelongated element along the axis of the stent structure, wherein thestent structure and the conductive elongated element are spaced adistance apart, and using the elongated element to provide a gas streamwithin the defined interior volume of the stent structure; and moving aplurality of coating particles towards the at least one surface of themedical device to form a coating thereon while the stent structure is ina vertical position such that the stent does not sag along its stentaxis.

A system for use in coating at least one surface of a medical deviceaccording to the present invention includes a particle source, a holdingfixture operable to position a medical device in a defined volume; and adispensing device configured to receive source material from theparticle source and dispense a plurality of monodisperse coatingparticles into the defined volume. The dispensing device includes one ormore nozzle structures, wherein each nozzle structure includes at leastone opening terminating at a dispensing end thereof from which aplurality of monodisperse coating particles having an electrical chargeapplied thereto is dispensed. The system further includes an electrodestructure that includes an electrode isolated from the dispensing endsof the one or more nozzle structures, wherein the electrode structure isoperable to create a nonuniform electrical field between the dispensingends of the one or more nozzle structures and the medical device for usein providing the plurality of monodisperse coating particles in thedefined volume. The plurality of monodisperse coating particles have anominal diameter of less than 10 micrometers and a geometrical standarddeviation of less than 1.2. Further, the nonuniform electric field isoperable to assist in moving a plurality of the coating particlestowards the at least one surface of the medical device to form a coatingthereon.

Another system for use in coating at least one surface of a stentstructure according to the present invention includes a particle sourceand a holding fixture operable to position a stent structure definedalong a stent axis in a defined volume, wherein the stent structureincludes at least an interior surface adjacent a defined interior volumeand at least an exterior surface. The system further includes adispensing device configured to receive source material from theparticle source and dispense a plurality of microdroplets having anelectrical charge associated therewith from the dispensing ends of theone or more nozzle structures into the defined volume, wherein each ofthe microdroplets includes at least a particle, and further wherein theelectrical charge is concentrated on the particles as the microdropletsevaporate resulting in a plurality of coating particles. Yet further,the system includes an electrode structure that includes an electrodeisolated from the dispensing ends of the one or more nozzle structures.The electrode structure is operable to create a nonuniform electricalfield between the dispensing ends of the one or more nozzle structuresand the stent structure for use in providing the plurality of coatingparticles in the defined volume and moving the plurality of coatingparticles towards the stent structure to form a coating on the at leastone surface thereof.

The systems described herein may also include one or more of thefollowing features: an electrode structure that includes a groundedmedical device; an electrode structure that includes a ring electrodepositioned forward of one or more nozzle structures; a dispensing deviceconfigured to dispense a spray of microdroplets having an electricalcharge associated therewith, wherein the electrical charge of themicrodroplet concentrated upon evaporation on the particle is greaterthan about 30 percent of the Rayleigh charge limit for the microdroplet;a dispensing device configured such that, prior to contact with the atleast one surface of a medical device, a residual particle volumeoccupied by an evaporated microdroplet includes less than about 20percent of a solvent component of the originally dispensed microdroplet;a holding fixture operable to position a medical device such that atleast one nozzle structure of the dispensing device is operable withinthe interior volume defined by a medical device structure; an electrodestructure operable to create a nonuniform electrical field between thedispensing end of the at least one nozzle structure and a medical devicefor use in providing the plurality of monodisperse coating particles inthe interior volume of the medical device; an elongated element sized tobe positioned or moved into the defined interior volume of a medicaldevice; a dispensing device that includes a plurality of nozzlestructures; a holding fixture configured to hold the medical device in afixed position within the defined volume; a holding fixture configuredfor movement of the medical device within the defined volume; a holdingfixture configured to receive a stent structure, wherein the stentstructure is defined along a stent axis and includes at least aninterior surface adjacent a defined interior volume and at least anexterior surface; a holding fixture configured to at least rotate thestent structure about the stent axis; a holding fixture configured to atleast move the stent structure linearly along the stent axis; a controlsystem operable to control the amount of monodisperse coating particlesprovided into a defined volume; a control system operable to adjust thestrength of the nonuniform electrical field; and a particle source thatincludes source material for use in providing a plurality of coatingparticles, wherein the source material includes at least onebiologically active ingredient or at least one coated biologicallyactive ingredient.

The systems described herein for coating a medical device may alsoinclude a holding fixture that includes an elongated substantiallynon-conductive tube for receiving the stent structure thereon and anelongated conductive element. At least a portion of the elongatedconductive element extends through the elongated substantiallynon-conductive tube, and further wherein the elongated conductiveelement comprises a conductive contact section. A compression apparatusis configured to provide for expansion of the elongated substantiallynon-conductive tube such that an exterior surface thereof is in contactwith at least a portion of the interior surface of the stent structureand such that a portion of the stent structure is in electrical contactwith the conductive contact section.

The systems described herein for coating a medical device may alsoinclude one or more of the following features: a dispensing device thatincludes an elongated cylindrical body member defining an interiorvolume thereof along an axis, wherein the holding fixture is operable toposition the stent structure along the axis of the elongated cylindricalbody member, and further wherein the one or more nozzle structures arepositioned radially about the axis of the elongated cylindrical bodymember and linearly along the elongated cylindrical body member in thedirection of the axis thereof; a plurality of nozzle structures thateach include a capillary tube comprised of a body portion and a taperedcapillary tip at the dispensing end of the capillary tube; a pluralityof the nozzle structures that each include a tapered portion used todefine an opening, wherein at least a part of each of the plurality ofthe nozzle structures extend from an integral conductive portionassociated with the body member; a plurality of the nozzle structuresthat each include a solid post along a center axis extending through anopening at the dispensing end; a plurality of the nozzle structures thatinclude an elongated radial opening in a body member; a plurality of thenozzle structures that include an elongated opening in the body memberlying parallel to an axis thereof; an elongated element extending alongan axis coinciding with the axis of a stent structure and spacingelements operable to maintain a distance between the stent structure andthe elongated element; a holding fixture that includes an elongatedelement sized based on the defined interior volume of the stentstructure such that a surface of the elongated element is in directcontact with the interior surface of the stent structure; a power sourceconfigured to create an electric field between a conductive elongatedelement and a stent structure that is opposite a nonuniform electricfield created between dispensing ends of nozzle structures and the stentstructure; and an elongated element configured to provide a gas streamwithin the defined interior volume of a stent structure.

Yet another system for use in coating at least one surface of a medicaldevice includes a particle generation apparatus operable to provide aplurality of coating particles in a defined volume and a holding fixtureoperable to position a stent structure defined along a stent axis in thedefined volume. The stent structure includes at least an interiorsurface adjacent an interior volume and an exterior surface. The holdingfixture includes an elongated element located within the interior volumeof the stent structure. The system further includes a temperaturecontrol apparatus operable to hold the elongated element at a lowertemperature than the temperature in the defined volume adjacent theexterior surface of the stent structure such that thermophoretic effectmoves the coating particles towards the at least one surface of thestent structure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a general diagram illustrative of a medical device coatingsystem, e.g., a nanoparticle generator system using electrospraytechniques for coating surfaces, in accordance with the presentinvention.

FIG. 2 is a general diagram of an illustrative embodiment of a stentstructure that can be coated according to the present invention.

FIG. 3 is a detailed portion of the stent structure of FIG. 2 coatedaccording to one or more embodiments of the present invention.

FIG. 4 is a general diagrammatical illustration of one embodiment of anelectrospray dispensing device including multiple nozzle structures foruse in a coating system shown generally in FIG. 1.

FIGS. 5A and 5B show a general diagrammatical illustration and a moredetail view of one portion thereof, respectively, of a configuration ofproviding multiple electrospray nozzle structures according to thepresent invention that may be employed in the coating system showngenerally in FIG. 1 according to the present invention.

FIGS. 6A and 6B show a general diagrammatical illustration and a moredetail view of one portion thereof, respectively, of another alternateembodiment of a configuration for providing multiple electrospray nozzlestructures that may be employed in the coating system shown generally inFIG. 1 according to the present invention.

FIGS. 7A and 7B show a general diagrammatical illustration and a moredetail view of one portion thereof, respectively, of yet anotheralternate electrospray multiple nozzle structure that may be employed inthe coating system shown generally in FIG. 1 according to the presentinvention.

FIGS. 8A and 8B show a general diagrammatical illustration and a moredetail view of one portion thereof, respectively, of yet anotheralternate configuration of a multiple nozzle structure that forms conejets for spraying particles using air as opposed to electrospraytechniques and which may be employed in the medical device coatingsystem of FIG. 1 according to the present invention.

FIGS. 9A-9E are a top view, a side view, and three additional moredetailed views of portions shown in the top and side views,respectively. The figures show a holding fixture that may be employed inthe medical device coating system shown generally in FIG. 1 according tothe present invention; particularly, the holding structure is beneficialin holding a stent structure to be coated.

FIGS. 10A and 10B are a perspective view and a cross-section view of aportion thereof, respectively, of one illustrative embodiment of amedical device coating system employing multiple nozzle structuresaccording to the present invention; the system being particularlybeneficial in coating stent structures.

FIGS. 11A and 11B show a perspective view and a cross-section view of aportion thereof, respectively, of another illustrative embodiment of acoating system employing multiple longitudinally configured nozzlestructures according to the present invention; the system beingparticularly advantageous in coating stent structures.

FIG. 12 is a perspective view of yet another alternate illustrativeembodiment of a coating system employing multiple radially configurednozzle structures according to the present invention; the system beingparticularly advantageous in coating stent structures.

FIGS. 13A-13C show yet another alternate configuration of a medicaldevice coating system according to the present invention. FIG. 13A is aperspective view of the medical device coating system. FIG. 13B is across-section view of a portion of the medical device coating systemshown in FIG. 13A. FIG. 13C is a more detailed view of a technique usedduring the coating process involving either electric field forces and/ormechanical forces such as those provided by air streams.

FIGS. 14A and 14B are perspective views used to illustrate a holdingstructure used during the coating of medical devices, particularly stentstructures, according to the present invention.

FIG. 15 is a perspective view of yet another alternate configuration ofa medical device coating system that may be employed for coating in theinterior volume of a medical device (e.g., coating interior surfaces ofa stent structure) according to the present invention.

FIGS. 16A and 16B show a perspective view and a cross-section view of aportion thereof, respectively, of another illustrative configuration ofa medical device coating system that employs the use of a thermophoreticeffect in coating a medical device according to the present invention.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The present invention shall generally be described with reference toFIG. 1. Various embodiments of the present invention shall then bedescribed with reference to FIGS. 2-16. It will become apparent to oneskilled in the art that elements from one embodiment may be used incombination with elements of the other embodiments, and that the presentinvention is not limited to the specific embodiments described hereinbut only as described in the accompanying claims. For example, one ormore different nozzle structures may be used for providing particlesused in the coating methods and systems.

The present invention provides for coated devices (e.g., coated stentstructures) and also systems and methods for coating objects, such asmedical devices. With use of the present invention, for example,coatings having uniform properties can be accomplished. Further, thepresent invention provides for the efficient and cost effective use ofcoating materials.

The present invention is directed to coating systems and methods thatemploy the generation of particles, such as, for example, nanoparticles,for use in coating objects. The present invention is particularlyadvantageous in the coating of medical devices (e.g., coating suchdevices with DNA, RNA, coated DNA particles, etc. As further describedbelow, the systems and methods according to the present invention mayuse one or more single nozzle electrospray apparatus such as thatpreviously described in U.S. Pat. No. 6,093,557 to Pui, et al., entitled“Electrospraying Apparatus and Method for Introducing Material intoCells,” issued 25 Jul. 2000 (e.g., single and dual capillaryconfigurations), and also described in the papers entitled,“Electrospraying of Conducting Liquids for Dispersed Aerosol Generationin the 4 nm to 1.8 μm Diameter Range” by Chen, et al., J. Aerosol Sci.,Vol. 26, No. 6, pp. 963-977 (1995), and entitled “ExperimentalInvestigation of Scaling Laws for Electrospraying: Dielectric ConstantEffect” by Chen, et al., Aerosol Science and Technology, 27:367-380(1997), or may use a multiple nozzle structure electrospray apparatussuch as described in U.S. Patent Application US-2002-0007869-A1,entitled “High Mass Throughput Particle Generation Using Multiple NozzleSpraying,” published on 24 Jan. 2002, which are all hereby incorporatedin their entirety by reference thereto. Further, other apparatus forgenerating particles, such as, for example, those described withreference to FIGS. 8A and 8B, may also be employed in one or moreembodiments described herein.

As shown in FIG. 1, the present invention provides a medical devicecoating system 10 employing a dispensing apparatus 15 to establish oneor more sprays of particles 22 (e.g., sprays of microdroplets whichevaporate to form sprays of particles). The dispensing apparatus 15includes one or more nozzle structures 20 which receive source material17 and establish sprays of particles 22 forward thereof, e.g., in thedirection of medical device 12. The particles 22 are moved toward atleast one surface 13 of the medical device 12 to form a coating 105thereon. The medical device 12 is preferably located in a defined volume(shown generally by the dashed line 11) where the particles 22 areprovided. The defined volume may, for example, be a reactor chamber, achamber of a stent coating system, a volume formed by a body member(e.g., as described with reference to FIG. 10), a vacuum chamber, apressurized and/or heated chamber, a volume of open air space, etc.

The dispensing apparatus 15 further includes a source holding apparatus16 for providing the source material 17 to the plurality of nozzlestructures 20 under control of control mechanism 14, e.g. hardwareand/or software control. Each of the one or more nozzle structures 20 isconfigured to provide a spray of particles 22 to the defined volume 11where the medical device is located. Generally, for example, in one ormore embodiments, such spray of particles 22 established forward of eachof the one or more nozzle structures 20.

The source material 17 held in the source holding apparatus 16 may beany source of material which can be provided in the defined volume inparticle form as described according to the present invention herein.Preferably, the source material 17 is a fluid composition that mayinclude a solution, a suspension, a microsuspension, an emulsion, amicroemulsion, a gel, a hydrosol, or any other fluid-like compositionsthat when provided according to the present invention results in thegeneration of particles. For example, such fluid compositions mayinclude a solution of dissolved active ingredients, e.g., drug activeingredients, according to one embodiment of the present invention.However, it is contemplated that the source material may also be a drymaterial, e.g., material having substantially no solvent or liquidcomponent associated therewith, as well.

As used herein, an active ingredient refers to any component thatprovides a useful function when provided in particle form, particularlywhen provided as nanoparticles. The present invention is particularlybeneficial for spraying nanoparticles and also is particularlybeneficial for spraying particles including biologically activeingredients.

As such, the term “active ingredient” refers to material which iscompatible with and has an effect on the substrate or body with which itis used, such as, for example, drug active ingredients, chemicalelements for forming nanostructures, and elements for film coatings,e.g., polymers, excipients, etc. The term “biologically activeingredient” or “biologically active material or component” is a subsetof active ingredient and refers to material which is compatible with andhas an effect (which may, for example, be biological, chemical, orbiochemical) on the animal or plant with which it is used and includes,for example, medicants such as medicines, pharmaceutical medicines, andveterinary medicines, vaccines, genetic materials such as polynucleicacids, cellular components, and other therapeutic agents, such as thosedescribed below.

As used herein, the term particle, and as such nanoparticle, includessolid, partially solid, and gel-like droplets and microcapsules whichincorporate solid, partially solid, gel-like or liquid matter. Particlesprovided and employed herein may have a nominal diameter as large as 10micrometers. As used herein, nanoparticle refers to a particle having anominal diameter of less than 2000 nm. The present invention isparticularly beneficial in spraying nanoparticles having a nominaldiameter greater than 1 nanometer (nm), and further preferably having anominal diameter less than 1000 nm, and more preferably less than 100nm.

Further, the particles used for coating medical devices described hereinare preferably monodisperse coating particles. As used herein,monodisperse coating particles are coating particles that have ageometrical standard deviation of less than 1.2. In other words, thestandard deviation with respect to mean particle size of particlesprovided according to the present invention is preferably less than orequal to 20%.

With further reference to FIG. 1, the method of coating at least aportion of a medical device 12 (e.g., surface 13 of medical device 12)shall be described. Generally, the medical device 12 is preferablypositioned within the defined volume 11 (e.g., the defined volume 11indicated generally by the dashed line that may be representative of achamber or other structure encompassing one or more elements of themedical device coating system 10). With the medical device 12 providedin the defined volume 11, the method of coating at least one surfacethereof may be initiated.

A plurality of coating particles 22 are provided in the defined volume11 (e.g., monodisperse coating particles 22). The coating particles 22are then moved towards at least one surface 13 of the medical device 12to form a coating thereon. The coating is represented generally as thedashed layer 105.

Depending upon the method used to move the coating particles 22 towardsthe at least one surface 13 of the medical device 12, the coatingparticles 22 may either be charged particles or uncharged particles. Forexample, if an electric field is used to move the coating particles 22towards the surface 13 of the medical device 12, then the coatingparticles 22 are charged particles, preferably, highly chargedparticles. On the other hand, if a thermophoretic effect is used to movethe coating particles towards the surface 13 of the medical device 12,then the coating particles may not need to be charged particles. Forexample, such uncharged particles may be provided using a dispensingapparatus such as that described with reference to FIGS. 8A and 8B, or,for example, electrosprayed according to the present invention andneutralized.

In different embodiments of the coating method according to the presentinvention, the coating particles 22 may be provided in the definedvolume 11 prior to or simultaneously with the movement of the coatingparticles 22 towards the surface 13 of the medical device 12. Forexample, highly charged particles may be provided in the defined volume11 prior to the establishment of an electric field utilized to move thecoating particles 22 towards the surface 13 of the medical device 12.Likewise, as is described herein, for example, an electric field may beestablished between the medical device 12 and the dispensing apparatus15 so as to simultaneously produce the particles 22 forward of thedispensing apparatus 15 and move such charged particles 22 towardssurface 13 of the medical device 12 (e.g., an electrode may bepositioned within an interior volume of the medical device 12 toestablish an electric field between the medical device 12 and thedispensing apparatus 15 or the medical device 12 may be grounded toestablish such an electric field therebetween).

Further, the medical device 12 and/or the dispensing apparatus 15 (orany component thereof) may be moved in any one or more differentdirections as represented generally by the horizontal/vertical movementarrows 101 and radial movement arrow 102 prior to, during, or after thecoating process for any particular reason. Such movement of the medicaldevice 12 or any elements of the coating system 10 may be performedusing any apparatus configured for the desired motion. The presentinvention is not limited to any particular structure for providing suchmovement. Further, the present invention is not limited to movement ofany elements of the coating system 10 or the medical device 12 duringthe coating process. In other words, for example, the medical device 12may remain in a fixed position within the defined volume 11 as thecoating process is performed.

As described above, the spray of particles 22 provided from the one ormore nozzle structures 20 are moved toward at least one surface 13 ofthe medical device 12. Such particles 22 are deposited onto the surface13 for coating purposes. As used herein, coating refers to forming alayer or structure on a surface. The coated layer or structure formed onthe surface may be a coating that adheres to an underlying layer or thesurface 13, or a coating that does not adhere to the surface or anunderlying layer. Any level of adherence to the surface 13 or anunderlying layer is contemplated according to the present invention. Forexample, a coating formed on surface 13 of the medical device 12 may beformed as a sheath about a structure (e.g., a stent structure) withoutnecessarily having adhesion between the layer and the medical device 12.

Likewise, an adhesion layer may be deposited on a medical device 12prior to forming a coating on the medical device 12 such that greateradhesion is accomplished. The adhesion layer may also be coated on thesurface 13 of the medical device 12 employing method and/or systemsaccording to the present invention.

Various embodiments of the coating methods and systems described aresuitable to allow one or more medical devices to be coated as a batch.However, the present invention is not limited to only coating medicaldevices in batches, i.e., coating a group of one or more devices in onebatch process followed by coating a second group of one or more devicesin a second batch process. The methods and systems of the presentinvention can be utilized to continuously run medical devices throughthe systems such that the process does not have to be started andstopped for coating the medical devices in batches. In other words, aplurality of medical devices can be coated through a continuous process.

In one or more of the embodiments of the present invention, single ormultiple coating materials can be applied to medical devices, separatelyor simultaneously. For example, a coating sprayed may include multiplecoating materials, different nozzle structures may be provided withdifferent source materials for controlling and spraying differentcoating materials, different nozzle structures may be controlled for useduring different time periods so as to provide different layers ofcoating materials on at least a portion of the medical device, multiplelayers may be sprayed using the same or different source materials(e.g., forming a somewhat laminated coating), the entire medical deviceor just a portion of the medical device may be coated (e.g., a chargecould be applied to a portion of the surface to attract all of or amajority of the sprayed particles to the charged portion), differentportions of the medical device may be sprayed with more coatingmaterials than the remainder of the medical device, and/or maskingmaterials may be used to mask certain portions of the medical devicefrom having coating applied thereto.

As indicated above, the present invention contemplates applying onelayer or multiple layers of the same or different coating materials.Such, layers may perform identical or different functions (e.g., toprovide for biocompatibility, to control drug release, etc.).

The medical devices used in conjunction with the present inventioninclude any device amenable to the coating processes described herein.The medical device, or portion of the medical device, to be coated orsurface modified may be made of metal, polymers, ceramics, composites orcombinations thereof, and for example, may be coated with one or more ofthese materials. For example, glass, plastic or ceramic surfaces may becoated. Further, the present invention may be used to form a coating onsurfaces of other objects as well, e.g., metal substrates or any othersurfaces that may be rendered conductive (e.g., whether flat, curved, orof any other shape).

Although the present invention is described herein with specificreference to a vascular stent, other medical devices within the scope ofthe present invention include any medical devices such as those, forexample, which are used, at least in part, to penetrate and/or bepositioned within the body of a patient, such as, but clearly notlimited to, those devices that are implanted within the body of apatient by surgical procedures. Examples of such medical devices includeimplantable devices such as catheters, needle injection catheters, bloodclot filters, vascular grafts, stent grafts, biliary stents, colonicstents, bronchial/pulmonary stents, esophageal stents, ureteral stents,aneurysm filling coils and other coiled coil devices, trans myocardialrevascularization (“TMR”) devices, percutaneous myocardialrevascularization (“PMR”) devices, lead wires, implantable spheres,pumps, etc., as are known in the art, as well as devices such ashypodermic needles, soft tissue clips, holding devices, and other typesof medically useful needles and closures. Any exposed surface of thesemedical devices may be coated with the methods and systems of thepresent invention including, for example, the inside exposed surface andthe outside exposed surface of a tubular medical device which is open atboth ends, e.g., a stent structure.

The coating materials used in conjunction with the present invention areany desired, suitable substances such as defined above with regard toactive ingredients and biologically active ingredients. In someembodiments, the coating materials comprise therapeutic agents, appliedto the medical devices alone or in combination with solvents in whichthe therapeutic agents are at least partially soluble or dispersible oremulsified, and/or in combination with polymeric materials as solutions,dispersions, suspensions, lattices, etc. The terms “therapeutic agents”and “drugs”, which fall within the biologically active ingredientsclassification described herein, are used interchangeably and includepharmaceutically active compounds, nucleic acids with and withoutcarrier vectors such as lipids, compacting agents (such as histones),virus, polymers, proteins, and the like, with or without targetingsequences. The coating on the medical devices may provide for controlledrelease, which includes long-term or sustained release, of a bioactivematerial.

Specific examples of therapeutic or biologically active ingredients usedin conjunction with the present invention include, for example,pharmaceutically active compounds, proteins, oligonucleotides,ribozymes, anti-sense genes, DNA compacting agents, gene/vector systems(i.e., anything that allows for the uptake and expression of nucleicacids), nucleic acids (including, for example, recombinant nucleicacids; naked DNA, cDNA, RNA; genomic DNA, cDNA or RNA in anon-infectious vector or in a viral vector which may have attachedpeptide targeting sequences; antisense nucleic acid (RNA or DNA); andDNA chimeras which include gene sequences and encoding for ferryproteins such as membrane translocating sequences (“MTS”) and herpessimplex virus-1 (“VP22”)), and viral, liposomes and cationic polymersthat are selected from a number of types depending on the desiredapplication. For example, biologically active solutes includeanti-thrombogenic agents such as heparin, heparin derivatives,urokinase, and PPACK (dextrophenylalanine proline argininechloromethylketone); prostaglandins, prostacyclins/prostacyclin analogs;antioxidants such as probucol and retinoic acid; angiogenic andanti-angiogenic agents; agents blocking smooth muscle cell proliferationsuch as rapamycin, angiopeptin, and monoclonal antibodies capable ofblocking smooth muscle cell proliferation; anti-inflammatory agents suchas dexamethasone, prednisolone, corticosterone, budesonide, estrogen,sulfasalazine, acetyl salicylic acid, and mesalamine, lipoxygenaseinhibitors; calcium entry blockers such as verapamil, diltiazem andnifedipine; antineoplastic/antiproliferative/anti-mitotic agents such aspaclitaxel, 5-fluorouracil, methotrexate, doxorubicin, daunorubicin,cyclosporine, cisplatin, vinblastine, vincristine, colchicine,epothilones, endostatin, angiostatin, Squalamine, and thymidine kinaseinhibitors; L-arginine, its derivatives and salts (e.g., argininehydrochloride); antimicrobials such as triclosan, cephalosporins,aminoglycosides, and nitorfurantoin; anesthetic agents such aslidocaine, bupivacaine, and ropivacaine; nitric oxide (NO) donors suchas lisidomine, molsidomine, NO-protein adducts, NO-polysaccharideadducts, polymeric or oligomeric NO adducts or chemical complexes;anticoagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGDpeptide-containing compound, heparin, antithrombin compounds, plateletreceptor antagonists, anti-thrombin antibodies, anti-platelet receptorantibodies, enoxaparin, hirudin, Warafin sodium, Dicumarol, aspirin,prostaglandin inhibitors, platelet inhibitors and tick antiplateletfactors; interleukins, interferons, and free radical scavengers;vascular cell growth promoters such as growth factors, growth factorreceptor antagonists, transcriptional activators, and translationalpromoters; vascular cell growth inhibitors such as growth factorinhibitors (e.g., PDGF inhibitor Trapidil), growth factor receptorantagonists, transcriptional repressors, translational repressors,replication inhibitors, inhibitory antibodies, antibodies directedagainst growth factors, bifunctional molecules consisting of a growthfactor and a cytotoxin, bifunctional molecules consisting of an antibodyand a cytotoxin; Tyrosine kinase inhibitors, chymase inhibitors, e.g.,Tranilast, ACE inhibitors, e.g., Enalapril, MMP inhibitors (e.g.,Ilomastat, Metastat), GP IIb/IIIa inhibitors (e.g., Intergrilin,abciximab), seratonin antagonist, and 5-HT uptake inhibitors;cholesterol-lowering agents; vasodilating agents; agents which interferewith endogenous vascoactive mechanisms; survival genes which protectagainst cell death, such as anti-apoptotic Bcl-2 family factors and Aktkinase; and combinations thereof; and beta blockers. These and othercompounds may be added to a coating solution, including a coatingsolution that includes a polymer.

Modifications to or various forms of the coating materials and/oradditional coating materials for use in coating a medical deviceaccording to the present invention are contemplated herein as would beapparent to one skilled in the art. For example, such coating materialsmay be provided in derivatized form or as salts of compounds.

Polynucleotide sequences useful in practice of the invention include DNAor RNA sequences having a therapeutic effect after being taken up by acell. Examples of therapeutic polynucleotides include anti-sense DNA andRNA; DNA coding for an anti-sense RNA; or DNA coding for tRNA or rRNA toreplace defective or deficient endogenous molecules. The polynucleotidesof the invention can also code for therapeutic proteins or polypeptides.A polypeptide is understood to be any translation product of apolynucleotide regardless of size, and whether glycosylated or not.Therapeutic proteins and polypeptides include, as a primary example,those proteins or polypeptides that can compensate for defective ordeficient species in an animal, or those that act through toxic effectsto limit or remove harmful cells from the body. In addition, thepolypeptides or proteins that can be incorporated into the polymercoating, or whose DNA can be incorporated, include without limitation,angiogenic factors and other molecules competent to induce angiogenesis,including acidic and basic fibroblast growth factors, vascularendothelial growth factor, hif-1, epidermal growth factor, transforminggrowth factor α and β, platelet-derived endothelial growth factor,platelet-derived growth factor, tumor necrosis factor α, hepatocytegrowth factor and insulin like growth factor; growth factors; cell cycleinhibitors including CDK inhibitors; anti-restenosis agents, includingp15, p16, p18, p19, p21, p27, p53, p57, Rb, nFkB and E2F decoys,thymidine kinase (“TK”) and combinations thereof and other agents usefulfor interfering with cell proliferation, including agents for treatingmalignancies; and combinations thereof. Still other useful factors,which can be provided as polypeptides or as DNA encoding thesepolypeptides, include monocyte chemoattractant protein (“MCP-1”), andthe family of bone morphogenic proteins (“BMP's”). The known proteinsinclude BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8,BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16.Currently preferred BMP's are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6and BMP-7. These dimeric proteins can be provided as homodimers,heterodimers, or combinations thereof, alone or together with othermolecules. Alternatively, or in addition, molecules capable of inducingan upstream or downstream effect of a BMP can be provided. Suchmolecules include any of the “hedgehog” proteins, or the DNA's encodingthem.

Coating materials other than therapeutic agents include, for example,polymeric materials, sugars, waxes, and fats, applied alone or incombination with therapeutic agents, and monomers that are cross-linkedor polymerized. Such coating materials are applied in the form of, forexample, powders, solutions, dispersions, suspensions, and/or emulsionsof one or more polymers, optionally in aqueous and/or organic solventsand combinations thereof or optionally as liquid melts including nosolvents. When used with therapeutic agents, the polymeric materials areoptionally applied simultaneously with, or in sequence to (either beforeor after), the therapeutic agents. Such polymeric materials employed as,for example, primer layers for enhancing subsequent coating applications(e.g., application of alkanethiols or sulfhydryl-group containingcoating solutions to gold-plated devices to enhance adhesion ofsubsequent layers), layers to control the release of therapeutic agents(e.g., barrier diffusion polymers to sustain the release of therapeuticagents, such as hydrophobic polymers; thermal responsive polymers;pH-responsive polymers such as cellulose acetate phthalate oracrylate-based polymers, hydroxypropyl methylcellulose phthalate, andpolyvinyl acetate phthalate), protective layers for underlying druglayers (e.g., impermeable sealant polymers such as ethylcellulose),biodegradable layers, biocompatible layers (e.g., layers comprisingalbumin or heparin as blood compatible biopolymers, with or withoutother hydrophilic biocompatible materials of synthetic or natural originsuch as dextrans, cyclodextrins, polyethylene oxide, and polyvinylpyrrolidone), layers to facilitate device delivery (e.g., hydrophilicpolymers, such as polyvinyl pyrrolidone, polyvinyl alcohol, polyalkyleneglycol (i.e., for example, polyethylene glycol), or acrylate-basedpolymer/copolymer compositions to provide lubricious hydrophilicsurfaces), drug matrix layers (i.e., layers that adhere to the medicaldevice and have therapeutic agent incorporated therein or thereon forsubsequent release into the body), and epoxies.

When used as a drug matrix layer for localized drug delivery, thepolymer coatings may include any material capable of absorbing,adsorbing, entrapping, or otherwise holding the therapeutic agent to bedelivered. The material is, for example, hydrophilic, hydrophobic,and/or biodegradable, and is preferably selected from the groupconsisting of polycarboxylic acids, cellulosic polymers, gelatin,polyvinylpyrrolidone, maleic anhydride polymers, polyamides, polyvinylalcohols, polyethylene oxides, glycosaminoglycans, polysaccharides,polyesters, polyurethanes, silicones, polyurea, polyacrylate,polyacrylic acid and copolymers, polyorthoesters, polyanhydrides such asmaleic anhydride, polycarbonates, polyethylene, polypropylenes,polylatic acids, polystyrene, natural and synthetic rubbers andelastomers such as polyisobutylene, polyisoprene, polybutadiene,including elastomeric copolymers, such as Kraton®,styrene-isobutylene-styrene (SIBS) copolymers; polyglycolic acids,polycaprolactones, polyhydroxybutyrate valerates, polyacrylamides,polyethers, polysaccharides such as cellulose, starch, dextran andalginates; polypeptides and proteins including gelatin, collagen,albumin, fibrin; copolymers of vinyl monomers such as ethylene vinylacetate (EVA), polyvinyl ethers, polyvinyl aromatics; other materialssuch as cyclodextrins, hyaluronic acid and phosphoryl-cholines; andmixtures and copolymers thereof. Coatings from polymer dispersions suchas polyurethane dispersions (BAYHDROL, etc.) and acrylic latexdispersions are also within the scope of the present invention.Preferred polymers include polyurethanes; polyacrylic acid as describedin U.S. Pat. No. 5,091,205; and aqueous coating compositions comprisingan aqueous dispersion or emulsion of a polymer having organic acidfunctional groups and a poly-functional crosslinking agent havingfunctional groups capable of reacting with organic acid groups, asdescribed in U.S. Pat. No. 5,702,754.

The release rate of drugs from drug matrix layers is largely controlled,for example, by variations in the polymer structure and formulation, thediffusion coefficient of the matrix, the solvent composition, the ratioof drug to polymer, potential chemical reactions and interactionsbetween drug and polymer, the thickness of the drug adhesion layers andany barrier layers, and the process parameters, e.g., drying, etc. Thecoating(s) applied by the methods and apparatuses of the presentinvention may allow for a controlled release rate of a coating substancewith the controlled release rate including both long-term and/orsustained release.

The coating material may include suspended particles, e.g., a powder.For example, the suspension particles may be fused to the surface of themedical device by an adhesion coating or some other technique such aselectrostatic phenomena.

The coatings of the present invention are applied such that they resultin a suitable thickness, depending on the coating material and thepurpose for which the coating or coatings are applied. For example,coatings applied for localized drug delivery are typically applied to athickness of at least about 1 micron and not greater than 30 microns.Preferably, the thickness is greater than 2 microns. Further,preferably, the thickness is not greater than 20 microns. In addition,very thin coatings such as those as thin as 100 Angstroms may beprovided. Much thicker coatings of more than 30 microns are alsopossible.

Preferably, according to the present invention, the medical device 12 isa stent structure. FIG. 2 shows one illustrative exemplary embodiment ofa stent structure 13. Stent structure 13 includes generally acylindrical body of open framework material 21 extending along an axis25. In other words, the material forming the stent structure 13 hasopenings 19 defined between portions of stent material 36 forming thestructure 13. Such open framework of material 21 is shown generally inFIG. 2 and only indicates that typical stent structures include stentmaterial and openings which form the structure. The present invention isnot limited to any particular stent construction. Generally, the stentstructure 13 extends along the axis 25 from a first open end 27 to asecond open end 29. The stent structure 13 generally includes anexterior surface 33 of the stent material 36 which generally facesopposite an interior surface 31 of the stent structure 13 which definesan interior volume between the first open end 27 and second open end 29thereof.

FIG. 3 generally shows an illustrative diagram of a portion of the stentstructure 13 of FIG. 2 as coated using the present invention. Forexample, the exterior surface 33 of the stent structure 13 may be coatedwith one or more layers 37. Likewise, the interior surface 31 adjacentthe interior volume of the stent structure 13 may be coated with one ormore coatings 23. For example, the exterior surface 33 may be coatedwith an adhesion layer and one or more therapeutic agents. For example,an anti-inflammatory therapeutic agent may be the final layer formed onthe exterior surface of the stent structure 13.

Further, for example, one or more layers 23 may be formed on theinterior surface 31 and may include, for example, an adhesion layeradjacent surface 31 with the final coating being in the form of ananti-coagulant biologically active ingredient.

One skilled in the art will recognize that FIGS. 2 and 3 are but oneillustrative and diagrammatical example of a stent structure that may becoated according to the present invention. The variety of differentstent structures are numerous and coating of any and all such structuresis contemplated according to the present invention (e.g., self expandingstructures, structures formed of material not in the form of openframework material, etc.). Further, it is also only illustrative of thenumber of layers that may be coated on any one surface of the stentstructure 13. For example, the actual coating applied by the presentinvention may take the form of a multi-layered laminate-type structurethat is adherent to one or more surfaces of the stent structure 13without any adhesion layer.

With further reference to FIG. 1, the nozzle structures 20 of thedispensing device 15 may include nozzle structures having any one ofvarious configurations and employing any number of different components,e.g., single and dual capillary electrodes, micro-machined taperedopenings, etc. For example, as previously indicated, such nozzlestructures may include one or more nozzle structures described in U.S.Pat. No. 6,093,557 or U.S. Patent Application US-2002-0007869-A1.Various types of nozzle structures, and dispensing devices with whichthey may be used, are shown and described herein. However, nozzlestructures described in documents incorporated herein may providefurther nozzle structures that may be used according to the presentinvention and/or may provide additional description regarding the nozzlestructures that have also been described generally herein.

For example, FIG. 4 shows one illustrative embodiment of an electrospraydispensing apparatus 52 that may be employed in the medical devicecoating system 10 such as shown generally in FIG. 1. The electrospraydispensing apparatus 52 includes one or more nozzle structures 54 forestablishing a spray of charged particles 68 from each nozzle structure54. The electrospray dispensing apparatus 52 includes a source materialholding apparatus 60 for providing source material 77 to each of thenozzle structures 54, e.g., simultaneously, for use in establishing thesprays of charged particles 68.

A single electrospray nozzle structure can deliver a controlled feedrate of source material in the establishment of a spray of particle 68within the envelope of the nozzle structure. This feed rate of sourcematerial can be increased by using the multiple nozzle structures 54bundled together in one or more various configurations. For example, thefeed rate may be increased by “n” times with “n” nozzle structures. Thepresent invention, as described further below, enables the employment ofas few as one nozzle structure and as many as, for example, 1,000 nozzlestructures, e.g., capillary tubes, within a small area, e.g., seven orten centimeter diameter.

One of various challenges in spraying highly charged nanoparticles froma tightly packed bundle of nozzle structures is to overcome the spacecharge effect of the nanoparticles from one nozzle structure on otheradjacent nozzle structures. With respect to various configurations ofmultiple nozzle structures, generally, the voltage required to form acone jet mode for a nozzle structure 54 increases with decreasinginternozzle distance. However, it is preferable to operate at a lowervoltage because higher voltages may cause arcing between nozzlestructures and a second electrode used to form the electric field; sucharcing being problematic. Therefore, it may be desirable to have amultiple nozzle structure configuration that can have nozzle structuresspaced close together with less internozzle distance, but which does notrequire a high voltage to establish the cone jet.

As shown in FIG. 4, each nozzle structure 54, e.g., a capillary tube 59,defines an opening 53 extending along an axis 51 and terminating atdispensing end 69. The opening 53 has a cross-section orthogonal to andcentered on the axis 51. As used herein, internozzle distance (L) isdefined as the distance between the center axis 51 of nozzle structures54.

The voltage required to obtain a cone jet operation varies based oninternozzle distance. Generally, in one embodiment, the voltage requiredto obtain cone jet operation for a single capillary tube 59 is about7500 volts. As the internozzle distance (L) decreases, a higher voltageis required to “expel” the highly charged nanoparticles away from thenozzle structure 54 to form the cone jet mode required for sprayingnanoparticles. Ultimately, the required voltage reaches the breakdownelectric field (approximately 18,000 volts) which defines the closestdistance for the internozzle spacing.

The internozzle distance (L) is also affected by the critical dimension(CD) of the opening 53, e.g., the diameter of cross-section of theopening 53 orthogonal to the axis 51 of the nozzle structure 54. Forexample, as shown in FIG. 4, capillaries 59 are provided along the axis51 of the nozzle structure 54 with each capillary terminating at adispensing end 69. The CD for the nozzle structure 54 is the diameter ofthe opening 53, i.e., the diameter of the cross-section of the openingfrom which spray is established at the dispensing end 69.

According to the present invention, to avoid the multiple nozzlestructures 54 from becoming a single electrode, e.g., arcing from thenozzle structures to the second electrode, a certain internozzledistance (L) must be provided between the nozzle structures 54.Preferably, according to the present invention, the ratio of theinternozzle distance (L) to CD, i.e., L/CD, is equal to or greater than2. In other words, as shown in FIG. 4, preferably, the ratio of theinternozzle distance (L) to the diameter of the opening 53 orthogonal toaxis 51 is equal to or greater than 2.

Each of the nozzle structures 54 of the electrospray dispensing device52 provides a charged spray with a high concentration of chargedparticles. Generally, the concentration of charged particles in thespray is in the range of about 10⁵ particles per cubic centimeter(particles per cc) to about 10¹² particles/cc. Due to the space chargeeffect, i.e., the effect created by the charge repulsion of chargedparticles, a spray of substantially dispersed particles having the samepolarity charge is provided with the particles distributed substantiallyuniformly across the spray area, as shown in FIG. 4.

As used herein, the term substantially dispersed particles refers touniformly and/or nonuniformly sized particles separated by an appliedrepulsive electrostatic force. Thus, the electrospray process is aconsistent and reproducible transfer process. Further, because thecharged particles of the spray repel one another, agglomeration of theparticles is avoided. This results in a more uniform particle size.“Substantially dispersed” particles is not to be confused withmonodisperse particles which involves the general degree of uniformityof the particles sprayed, e.g., the standard deviation of the particlesfrom a nominal size.

Generally, according to the configuration as shown at FIG. 4, the chargeis applied by concentration of charge on the spray of particles throughevaporation of solution including the material, e.g., active ingredient,in an established electrical field 79. In other words, for example, thesource material 77 may be a suspension of active ingredients or asolution including dissolved active ingredients. The suspension orsolution is then dispensed from the electrospray dispensing device 52,e.g., active ingredient of microdroplets are dispensed. In other words,the liquid sprayed generally evaporates to concentrate a charge of aliquid portion thereof on the particles, e.g., active ingredientparticles, in the fluid composition or suspension being sprayed. Thisresults in the spray of charged particles 68 as described further below.

FIG. 4 generally shows a diagrammatical illustration of the operation ofthe electrospray dispensing apparatus 52 for establishing charge sprays68 from each of the nozzle structures 54. Each of the nozzle structures54 receives a flow of fluid composition from the material source holdingapparatus 60. For example, the material source holding apparatus 60 mayinclude a fluid composition 77 suspending drug active ingredients orhaving active ingredients dissolved therein.

Generally, a conductive material 56, e.g., a conductive plate, positionseach of the nozzle structures 54 in a particular configuration. Theconductive material 56 is adapted to be connected to a high voltagesource 73. Each of the nozzle structures 54 includes a conductivestructure, e.g., a capillary tube 59 as illustratively shown in FIG. 4,defining an orifice, e.g., an opening 53 (e.g., a capillary tube openingor an orifice defined in a flooding type chamber, etc.) for receiving aflow of fluid composition 77 therein.

Although various configurations for the source material holdingapparatus 60 may be used according to the present invention, preferablya single holding apparatus is used to feed fluid composition 77 to oneor more of the nozzle structures 54. One will recognize that any numberof different and separate holding apparatus may be used or hold variousdifferent fluid compositions and provide different compositions todifferent nozzle structures 54.

Preferably, the fluid composition 77 may be pushed or pulled through theopening 53 and provided at dispensing end 69 of the nozzle structure 54,e.g., pushed by a pump. Preferably, a compressed gas source representedgenerally by arrow 64, e.g., an inert source that is non-reactive withthe fluid composition 77, is provided to compress the fluid composition77 and force fluid to flow through openings 53 of the nozzle structures54. Although, preferably, a compressed gas source 64 is used to providesuch fluid composition flow, other methods of providing such flow mayalso be used. For example, a plate above the fluid composition 77 havinga force, e.g., pneumatic force, applied thereto may be used, or syringepumps for each nozzle structure may be used.

The nozzle structures 54 positioned by and electrically coupled to theconductive structure 56 function as a first electrode of theelectrospray dispensing device 52 with the dispensing ends 69 of eachnozzle structure being positioned for dispensing charged microdropletstoward medical device 12, or a surface 13 thereof. In the exemplaryembodiment of FIG. 4, to set up the electric field 79, the medicaldevice 12 functions as a second electrode structure, e.g., a groundedmedical device 12 as shown by ground 81. An electrical potentialdifference is applied between the first electrode conductive structure56 and the second electrode or grounded medical device 12 that iselectrically isolated from the first electrode. One skilled in the artwill recognize that the electrodes may be formed using one or moreconductive elements, and such electrodes may take one of variousdifferent configurations.

Generally, in operation, a flow of the fluid composition 77 is providedthrough the openings 53 of the nozzle structures 54, e.g., pushed and/orpulled through the openings 53. A meniscus is formed at the dispensingend 69 where the opening 53 has a diameter in the preferred range ofabout 6 microns to about 2 millimeters. A potential difference isapplied to establish a nonuniform field 79 between the first electrodeconductive structure 56 electrically coupled to the nozzle structures 54and the second electrode (e.g., the medical device 12) connected toground 81. For example, a high positive voltage may be applied to thefirst electrode conductive structure 56 with the second electrodemedical device 12 being grounded. Further, for example, a voltagedifference that provides an electric field intensity of greater than 4kV/cm is preferably used.

As used herein, nonuniform electric field refers to an electric fieldcreated by an electrical potential difference between two electrodes.The nonuniform electric field includes at least some electric fieldlines that are more locally concentrated at one electrode relative tothe other electrode, e.g., more concentrated at the dispensing end 69relative to the second electrode or a grounded medical device 12. Inother words, for example, at least some of the field lines are off axisrelative to the longitudinal axis 51 through the center of the opening53. Further, for example, the grounded medical device 12 is positionedforward of dispensing end 69 and is of a size and/or includes at least aportion that is located at a position away from the longitudinal axis51. In various embodiments, the second electrode may be one or more ringelectrodes, plate electrodes, grounded medical device surfaces, etc. Themedical device 12 may still be coated even if a different electrodestructure is used to produce the charged particles.

For example, a ring electrode may be positioned forward of thedispensing end 69 to create the electric field for providing highlycharged particles in the defined volume in which the medical device ispositioned. With the particles provided in the defined volume, anotherelectrical field may be created to move the highly charged particlestoward a grounded medical device. As such, it will be recognized thatcoating the medical device 12 using the coating system 10 showngenerally in FIG. 1 may involve providing particles in a defined volumein which the medical device is provided, and thereafter, moving theparticles toward the medical device for forming a coating thereon. Inaddition, alternatively, the particles may be formed and moved towardthe medical device for coating thereon simultaneously with theirformation. For example, the medical device may be grounded to set up theuniform field for producing the charged particles in the defined volumein which the medical device is provided with the field also providingfor the movement of such charged particles towards the medical device 12so as to form a coating thereon.

In one exemplary embodiment, where the fluid composition includes anactive ingredient, the fluid composition 77 is flowed through theopening 53 of the nozzle structures 54. Generally, the fluid composition77 provided to the opening 53 has an electrical conductivity. As thefluid composition 77 progresses through the opening or orifice 53, thepotential difference between the first and second electrodes whichcreates the electric field therebetween strips the liquid of onepolarity of charge, i.e., the negative charge is stripped when a highpositive voltage is applied to the electrode 56, leaving a positivelycharged microdroplet to be dispensed from the dispensing end 69. Forexample, the meniscus at the dispensing end 69 may form a cone jet fordispensing a spray of microdroplets including the active ingredientswhen forces of a nonuniform field balance the surface tension of themeniscus. The spray of microdroplets further become more positive in anonuniform electric field.

As the microdroplets evaporate, the charge of the microdropletsconcentrate on the active ingredients resulting in a spray of chargedparticles. The amount of charge on the microdroplet, and thus the amountof charge on a particle after evaporation, is based at least upon theconductivity of the fluid composition used to spray the microdroplet,the surface tension of the fluid composition, the dielectric constant ofthe fluid composition, and the feed flow rate thereof. Preferably, theelectric charge concentrated on a particular particle is greater thanabout 30% of a maximum charge that can be held by the microdroplets,without the microdroplet being shattered or torn apart, i.e., greaterthan about 30% of the Rayleigh charge limit. Preferably, the charge isgreater than 50% of the Rayleigh charge limit. At 100%, the surfacetension of the microdroplet is overcome by the electric forces causingdroplet disintegration. The nonuniform electric field also provides forcontainment of particles and/or direction for the particles which wouldotherwise proceed in random directions due to the space charge effect.

One skilled in the art will recognize that the voltages applied may bereversed. For example, the first electrode may be grounded with a highpositive voltage applied to the second electrode. In such a case, theparticles would have a negative charge concentrated thereon. Further,any other applied voltage configuration providing a nonuniform electricfield to establish the charged spray of particles may be used.

The nonuniform electric field can be provided by various configurations.For example, the second electrode may be any conductive materialgrounded and positioned to establish the formation of a spray 68 fromthe dispensing ends 69 of the nozzle structures 54, e.g., the secondelectrode may be a grounded ring electrode, a grounded elongated elementpositioned in the interior volume of a stent structure, etc. The secondelectrode may also be located at various positions, such as just forwardof the nozzle structures 54, or located farther away from the nozzlestructures 54 and closer to medical device 12.

The strength of the field may be adjusted by adjustment of the distancebetween the first and second electrodes. Different field strengths mayresult in relatively different areas D upon which particle spray isprovided, at least in part due to the space charge effect of the spraysof particles 68. One skilled in the art will recognize that one or morecomponents of the dispensing apparatus 52 may be moved relative to theothers, e.g., the medical device relative to the one or more nozzlestructures 54 or vice versa, to facilitate adjustment of field strength.

The fluid composition 77 from the holding apparatus 60 is provided tothe nozzle structures 54, when operable, under control of, preferably,compressed gas source 64. As described above, the flow may also becontrolled with use of a liquid pump (e.g., a syringe pump, a gravityfeed pump, a pressure regulated liquid reservoir, etc.), a mass flowcontroller, or any other flow control devices suitable for feedingsource material, e.g., fluid composition 77, to the one or more nozzlestructures 54 as would be known to one skilled in the art.

The flow of fluid composition is atomized into microdroplets by thedispensing device 52. Atomization may be provided by any known techniquefor producing microdroplets, which microdroplets preferably have anominal diameter of about 10 nanometers or greater, more preferablyabout 20 nanometers to about 10 micrometers, and even more preferablyabout 30 nanometers to about 1 micrometer. Preferably, electrostaticatomization is used. However, other atomization devices (e.g., pressureregulated atomizers, ultrasonic nebulizers, hydraulic nozzles, etc.) mayprovide adequate atomization. As described previously herein,microdroplets having nominal diameters in the range of about 10nanometers to about 2 microns can be produced by electrospray. Variousfactors as described in such references affect the produced dropletsize. For example, capillary size, liquid feed rate, the dispensingdevice, surrounding gas properties, etc. One skilled in the art willrecognize that such factors and others may be modified to control andproduce microdroplets of various desired sizes.

By applying different electrical potential differences between themultiple nozzle structures 54, e.g., capillary tube electrodes 59, andthe second electrode, different operating modes can be established. Forexample, a high positive voltage 73 applied to the capillary tubeelectrodes via the conductive structure 56 with the grounding of thesecond electrode medical device 12 provides sprays 68 with a relativelyhigh positive charge. The second electrode 12 in such a case may beprovided to ground 81 or may have a negative voltage connected thereto.For example, the voltage applied is limited by the maximum electricfield intensity permitted in the medium in which the field is created.For example, arcing will occur in air at an electrical field intensitygreater than about 30 kV/cm. However, the allowed electric fieldintensity can be increased with use of a sheath gas about the nozzlestructures, such as CO₂, SF₆, etc.

With relatively large potential differences being applied, as describedherein and in other documents cited herein, pulsating modes or cone jetmodes of operation are achieved. In a cone jet mode of operation, a coneshaped liquid meniscus is formed at the dispensing end 69, whereas inthe pulsating mode, the shape of a liquid meniscus alternates between acone shape and a round shape. On the other hand, with relatively lowelectrical potential differences applied between the capillary tubeelectrode 59 and the second electrode 12, dripping from the dispensingtip occurs. According to the present invention, a spray from a cone jet83 formed at the orifice or opening 53 of the capillary tube 59 ispreferred.

Although various configurations, as described further below, for theelectrospray dispensing apparatus may be suitable, the dispensingapparatus 52 preferably includes capillary tubes 59 made of a suitablematerial, such as, for example, platinum, silica, etc., for providingthe spray 68 from each of the nozzle structures 54, e.g., the capillarytube 59 thereof. For example, the capillary tube may have an outerdiameter in the preferred range of about 6 micrometers to about 2.5millimeters and an inner diameter in the preferred range of about 6micrometers to about 2 millimeters.

Further, the dispensing apparatus 52 may include a casing about eachcapillary tube, e.g., a concentric tube, or about the dispensingapparatus 52, e.g., a housing surrounding the spraying portion of theapparatus 52, which may be used to provide a sheath of gas, e.g., CO₂,SF₆, etc., around the capillary tubes 59 to increase the electrostaticbreakdown voltage for the capillary tubes, e.g., to prevent coronadischarge. The use of such a sheath of gas is particularly beneficialwhen the spray is created using a high surface tension liquid, e.g.,deionized water.

As previously mentioned, the nonuniform electric field provides forcontainment of particles and/or direction for the particles which wouldotherwise proceed in random directions due to the space charge effect;the space charge effect being necessary to provision of monodisperse andnonconglomerated particles. The space charge effect is generallydependent upon the size of the particles and the charge thereon. Withthe electric field being utilized to move the particles towards themedical device 12 and preventing them from scattering to otherlocations, the amount of coating material necessary to coat the medicaldevice is substantially reduced.

For example, such a reduction in the amount of coating material can beclearly understood from a comparison between coating according to thepresent invention and the dipping of a medical device. In the dippingprocess, a reservoir having the coating material therein must beprovided for allowing the device to be dipped. The quantity of materialrequired for dipping is quite substantial.

Contrary to the dipping process, according to the present invention, forexample, the concentration of the particles in the defined volume can becontrolled with only adequate coating material being present which is todeposited on the medical device. As such, the quantity of coatingmaterial (e.g., DNA or RNA) required is substantially less than requiredfor dipping. In addition, the electric field directs the particlestowards the medical device 12 and prevents the particles from depositingon structures surrounding the medical device, e.g., walls of a chamberin which the medical device is positioned, and other structures that maybe used in the coating of the medical device such as apparatusassociated with the movement of the medical device 12, e.g., eitherlongitudinally or radially.

Further, as described above, as the microdroplets evaporate, the chargeof the microdroplets concentrate on the active ingredients resulting ina spray of charged particles. Preferably, the coating material system 10is configured such that prior to contact with the at least one surface13 of the medical device 12, a residual particle volume occupied by theevaporated microdroplet includes less than about 20% of a solventcomponent of the microdroplet sprayed from the dispensing apparatus.However, preferably, some solvent component forms a part of the residualparticle volume as the particle contacts the surface 13 of the medicaldevice 12. With some solvent component being a part of the residualparticle volume occupied by the evaporated microdroplet, adhesion of themicrodroplet (including the particle) to the surface 13 of the medicaldevice 12 may be enhanced. After the microdroplet which includes lessthan about 20% of the solvent component of the originally sprayedmicrodroplet has contacted the surface 13 of the medical device, theremainder portion of the solvent evaporates, leaving the particle coatedon the surface 13 of the medical device 12. In other words, prior tocontact with the at least one surface 13 of the medical device 12, theresidual particle volume occupied by the evaporated microdropletincludes some solvent component but less than about 20% of a solventcomponent contained in the originally sprayed microdroplet.

The amount of evaporation prior to the microdroplet/particle contactingthe surface 13 of the medical device 12 may be controlled in any numberof different ways. For example, the evaporation may be controlled by thetype of solvent used, the distance between the dispensing apparatus andthe medical device, the temperature and pressure of a chamber in whichthe medical device is provided, the size of the microdroplet, etc. Thepresent invention is not limited to any particular method of controllingsuch evaporation, and various other methods will be apparent to thoseskilled in the art.

Various configurations of the one or more nozzle structures 54 may beused. For example, the various configurations may include the use of asingle capillary tube, multiple capillary tubes bundled in one or moredifferent configurations such as, for example, a pentagon shape, hexagonshape, or other spatial configurations as described in U.S. PatentApplication US-2002-0007869-A1, published on 24 Jan. 2002.

Further, for example, capillary tubes made of a suitable material, suchas, for example, platinum, silicon, etc., may be used for providingsprays of particles as described herein. Preferably, such capillarytubes are tapered at the tips thereof so as to concentrate the electricfield at the tip of each capillary.

Use of capillary tubes may include the use of a single capillary tube aswell as dual concentric capillary tubes, such as described in theabove-mentioned U.S. Patent Application, US-2002-0007869-A1. Forexample, dual streams of liquids may be provided from a concentric dualopening capillary dispensing end for establishing a spray from thedispensing apparatus. A dual capillary configuration may be used tospray coated particles of active ingredients or create particles havingmore than one ingredient. For example, active ingredients may beprovided by a first fluid composition through a first opening and acoating material, e.g., a time release polymer, may be provided by asecond fluid composition through a second opening. For example, whensprayed, the coating material may encapsulate the active ingredient, atleast in part, and the coated particles are then transported for forminga layer on the medical device 12.

Further, such a dual capillary configuration may be used to controlconductivity of the particle being sprayed by changing the electricalconductivity of one or more of the liquids being sprayed (e.g.,increasing the conductivity of one of the compositions being sprayedsuch that a higher charge is concentrated on the particle duringevaporation).

In addition to the use of fluids with different conductivity, the fluidsmay also have a different surface tension. For example, a fluid may beflowed through a center capillary with the other fluid being provided inthe space between the center capillary and a concentric capillary asdescribed in U.S. Patent Application, US-2002-0007869-A1. With the useof two different fluids having different conductivity and surfacetension, hard to spray fluids through the center capillary can beprovided at the dispensing ends of the center and concentric capillary.Such spraying is facilitated by, for example, the additionalconductivity of the fluid (e.g., an alcohol) in the space surroundingthe center capillary such that additional charge is concentrated on theparticles sprayed through the center capillary. The spraying is alsoassisted by the surface tension differences between the fluids as theymeet at the dispensing end of the dual capillary configuration to formthe cone jet for spraying the fluid through the center capillary.

The dual capillary configuration may be used with any type of sourcematerial. For example, the fluids may be active ingredients,biologically active ingredients, excipients, or any other sourcematerials such as those described herein.

Further, the outer fluid may be in a gas form to assist in forming acone jet or providing components for use in spraying material from thecenter capillary. Such a gas may also be provided by the centercapillary with a fluid provided in the space between the center andconcentric capillaries. In such a manner, particles having voids at thecenter may be formed. Such a particle defining a void, e.g., a bubble,may be beneficial in, for example, a situation where surface area isdesired but the quantity of ingredient forming the larger surface areais to be kept to a minimum.

Clearly the present invention is not limited to the use ofcapillary-type nozzle structures as various suitable nozzle structuresmay be employed. For example, various other nozzle structures aredescribed generally herein. Any nozzle structure suitable to provide aspray of particles according to the principles described herein may beused, e.g., slits that may provide various cone jets (e.g., with orwithout posts as described herein), nozzle structures having portionsthereof that are integral with portions of other nozzle structures,nozzle structures that form a part of a chamber wall in which a medicaldevice is positioned, radially or longitudinally configured slots suchas described herein with particular reference to coating stentstructures as shown in FIGS. 11-13, multiple opening nozzle structures(e.g., micromachined nozzle structures that each have dual openings likethat of the dual capillary configuration), etc.

In one of the many different possible nozzle structure implementations,the nozzle structures may be provided using a configuration shown inFIGS. 5A and 5B. An electrospray dispensing apparatus 502 that may beemployed in the medical device coating system of FIG. 1 includes one ormore nozzle structures 506. The nozzle structures 506 are provided,preferably, by a single integral conductive material 504, e.g., amicro-machined plate. The conductive material or micro-machined plate504 may form a part, e.g., the bottom surface 523, of fluid compositionholding apparatus 522 for containing fluid composition 524 and providinga flow of fluid composition 524 to each of the nozzle structures 506.For example, as described previously herein, a compressed gas source 526may be used to deliver the fluid composition 524 to each orifice oropening 525 of the nozzle structures 506. With a potential differenceprovided between the conductive material 504, in which the multiplenozzle structures 506 are formed, and the medical device 520, cone jets517 (see FIG. 5B) are provided at dispensing ends 513 of the one or morenozzle structures 506 to provide the sprays of particles 519 (e.g.,microdroplets that evaporate and concentrate charge on the containedparticles used to coat the medical device).

FIG. 5B shows one of the nozzle structures 506 of FIG. 5A in furtherdetail. The nozzle structure 506 includes a tapered portion 516 thatdefines the orifice or opening 525. The opening 525 of the nozzlestructure 506 extends along the axis 501. The tapered portion 516includes tapered inner surfaces 509, i.e., inner relative to the fluidcomposition, to receive fluid composition 524 and provide sufficientflow into opening 525. The tapered portion 516 further includes outertapered surfaces 508. The outer tapered surfaces 508 and inner taperedsurfaces 509 are preferably opposing surfaces having a generallyparallel configuration. In other words, such tapers are at the sameangle relative to the generally plate-like conductive material 504 whichlies orthogonal to axis 501. The tapered outer surfaces 508 extendtowards the target 520 and terminate at dispensing end 513 at which acone jet is formed when operating under the applied potentialdifference.

FIGS. 6A and 6B show a diagrammatic illustration of another alternateembodiment of an electrospray dispensing apparatus 552 that includes oneor more nozzle structures 556 in a similar manner to that shown in FIGS.5A and 5B, but having a dual opening configuration. In such a manner,this apparatus may be used in a manner similar to that described hereinwith respect to concentric capillaries and also as described in U.S.Patent Application, US-2002-0007869-A1.

As shown in FIG. 6A, the dispensing apparatus 552 includes generally twoconductive plate-like structures 584 and 585 acting as the firstelectrode of the device 552. The conductive plate-like structures 584and 585 are separated to allow for a fluid composition 573 to beprovided therebetween from a fluid composition source 572. Theplate-like structures 584 and 585 are formed to provide the dual openingnozzle structures 556. Each of the nozzle structures 556 form a cone jet560 upon application of a suitable potential difference between thefirst electrode, i.e., the conductive plate structures 584 and/or 585and the medical device 554. As such, a spray of particles 562 isprovided or established at the dispensing ends 582 (see FIG. 6B) of eachnozzle structure 556.

Once again under application of compressed gas 568, fluid composition566 held in holding apparatus 564 is provided for flow through each ofthe nozzle structures 556. The fluid composition 566 may be the same ordifferent than the fluid composition 573. Preferably, the fluidcomposition 566 is different than the fluid composition 573. Forexample, as previously described herein, fluid composition 566 mayinclude an active ingredient for medicinal purposes and the fluidcomposition 573 may include an excipient or a coating material, such asa time release material, e.g., a polymer. With the use of such fluidcompositions, coated particles can be sprayed from each nozzle structure556 for use in coating the medical device 554.

FIG. 6B shows a more detailed drawing of one nozzle structure 556employed in the dispensing device 552. As shown in FIG. 6B, firstconductive plate structure 584 provides for the definition of an opening596 through which first fluid composition 566 is provided. The firstconductive plate structure 584 and the second plate structure 585provide for a space or channel 570 therebetween to receive a secondfluid composition 573. The second fluid composition 573 meets the firstfluid composition 566 at opening 594 defined by the second conductiveplate structure 585. Depending on the configuration defining theopenings 594, 596 and channel 570, the two fluid compositions may comeinto contact with each other in either the channel 570 or the opening594.

The first conductive plate structure 584 includes a tapered portion 586that defines the opening 596 along axis 553. The tapered portion 586includes inner tapered surfaces 598, i.e., relative to fluid composition566, that receive fluid composition 566, and outer surfaces 597 taperedin a manner, preferably like those of inner surfaces 598. The outersurfaces 597 extend towards the medical device 554 and terminate at anoutlet 574 into channel 570.

Likewise, conductive plate structure 585 includes tapered portion 588which defines opening 594 along axis 553. The tapered portion 588includes inner surfaces 591 that receive the second fluid composition573 and the first fluid composition 566 provided via outlet 574. Thetapered portion 588 further includes outer tapered surfaces 590 thatterminate at dispensing end 582 such that when a potential difference isapplied between the conductive plate structures 585, 588 and the medicaldevice 554, a cone jet 560 is formed at the dispensing end 582.

It will be recognized that drilling simple holes in conductive plateswill not provide for the formation of a cone jet at an orifice thereof.As shown in FIGS. 5 and 6, to form a cone jet at the dispensing ends ofthe nozzle structures shown therein, each of the nozzle structures mustinclude a protrusion from a plate-like structure. In other words, thetapered portions of the nozzle structure shown in FIGS. 5-6 whichprovide a protrusion or extension from such plates are required to allowfor the formation of a cone jet at the tip of such protrudingstructures.

As shown in FIGS. 5 and 6, the openings may take the form of a smallcapillary tube type opening or may take the form of an elongated opening(i.e., a slot). For example, with reference to FIGS. 5A and 5B, theopenings 506 and 556 may take the form of elongated openings such asshown in the embodiments for coating a stent structure. For example, oneembodiment shown in FIG. 11 uses elongated longitudinal slots that arepositioned parallel to an axis along which the stent structure islocated. A plurality of the longitudinal slots are located radiallyabout the axis. Radially configured slots are shown in FIG. 12. Suchradially configured slots are formed at a distance radially from theaxis along which the stent structure is located. A plurality of theradially configured slots (e.g., arcs) are spaced along the axis.

As previously described herein, the particles, e.g., nanoparticles ofthe sprays established at the dispensing ends of the nozzle structuresare generally highly charged which occurs because of an increasinglyhigher voltage potential applied to the nozzle structure to operate incone jet mode. Because of the increasingly higher voltage potential,eventually, a corona discharge and voltage breakdown may occur anddestroy the cone jet. As shown in FIG. 6A, it is possible to use aseparation structure, e.g., structure 558, to isolate each nozzlestructure from adjacent nozzle structures to reduce the space chargeeffect caused by the highly charged nanoparticles. This separationstructure technique provides one method of allowing the nozzlestructures to be highly packed into a small region.

Various configurations for the separation structure 558 may be used. Forexample, when capillary tubes are used, separation structures extendingfrom a plate are provided between each of the capillaries and may beused as described in U.S. Patent Application, US-2002-0007869-A1. Oneskilled in the art will recognize that any form or size of suchseparation structure may be used as long as suitable isolation of thedispensing ends from each other is provided. Generally, and preferably,the separation structures extend to a point lower than the dispensingend or, in the conjunction with the use of capillaries, the tipsthereof. In such a manner, a cone jet is allowed to form at thedispensing end of each nozzle structure.

The separation structure may be made of any insulative material, such asTeflon, plastic, etc. Because the space charge effect is reduced by theseparation structure, i.e., the space charge effect between nozzlestructures, a more uniform dispersed spray of particles is provided.This is in part due to the lower voltage operation allowed with the useof such separation structure.

It will be recognized by one skilled in the art that the configurationof the separation structure will be, at least in part, dependent uponthe structure or configuration of the nozzle structures. In other words,if a rectangular pattern of nozzle structures is utilized, then linetype separators may be used. Likewise, if a circular configuration ofnozzle structures is used, then such separators may need to be in a typeof circular configuration.

Separation structures are shown in FIG. 6A. Such separation extensions558 are shown as extending from conductive plate structure 585 toseparate the nozzle structures 556. Likewise, as shown in FIG. 5A,separation extensions 512 extend from conductive plate structure 504 toseparate the nozzle structures 506.

Another alternate dispensing device 700 is shown in FIGS. 7A and 7B. Inthis alternate configuration, axial posts 716 are used to guide liquidflow. Cone jet formation is facilitated by having the guided post 716 atthe center of the cone jet 720. FIG. 7A shows an exemplary side view ofthe dispensing device 700 and FIG. 7B shows a cross-section of FIG. 7Aat line 7B-7B.

As shown in FIGS. 7A and 7B, the dispensing device 700 includes aconductive plate 706 having multiple openings 712, e.g., circularopenings, formed therein for use in providing multiple nozzle structures708. Each opening 712 and the conductive plate 706 generally lieorthogonal to axes 701 of the nozzle structures 708. For machiningpurposes, such openings may be connected by channel portions 714.

Each of the nozzle structures 708 is formed using one of the openings712 by providing a post member 716, e.g., a solid post, along the axis701 through the center of the opening 712. The post member 716 includesa tip 721 that extends a predetermined distance past the conductiveplate 706 and through the opening 712 to form the nozzle structure 708.

The plate structure 706 may form a part of fluid composition holdingapparatus 704 in which fluid composition 702 is contained. As the fluidcomposition 702 is pushed through openings 712 forming part of thenozzle structure 708, by or under control of, for example, a compressedgas source 730, the fluid composition 702 follows the post 716. With theappropriate pressure applied by gas source 730 and an electricalpotential difference applied between the plate 706 and medical device710, cone jets 720 are formed at the tips 721 of the post members 716.Sprays of particles 722 are then provided as a result of the cone jets.

The particles in one or more embodiments of the medical device coatingsystem 10 according to the present invention may be provided in one ormore different manners according to the present invention. For example,as previously described in many of the embodiments, charged particlesare provided by an electrospray apparatus. However, in some embodiments,the particles do not need to be charged particles.

For example, as further described below, use of an thermophoretic effectmay be used to move coating particles towards the medical device 12 forcoating a surface 13 thereof. In such a case, an alternative toproviding a cone jet by electrostatic force is used to form the conejet. The alternative technique uses an aerodynamic force to provide thecone jet for spraying the particles. FIGS. 8A and 8B show an airdispensing apparatus 800 that employs the use of aerodynamic force inthe formation of a cone jet which may be employed in the generalembodiment of the medical device coating system shown in FIG. 1.

The air dispensing apparatus 800 includes a plate 840 having openings842 formed therein for use in providing multiple nozzle structures 806.The multiple nozzle structures 806 of the air dispensing device 800 areprovided by positioning a capillary 812 with an end 815 thereof in closeproximity to the opening 842 in the plate 840. The capillary 812generally lies orthogonal to the plate 840. In such a configuration, andas further described below with reference to FIG. 8B, a cone jet 831 canbe formed at the dispensing end 810 of the nozzle structure 806 toprovide a spray of particles 808 from each nozzle structure 806 that canbe moved toward the medical device 804 to form a coating thereon.

To form the cone jet 831, a fluid composition 822 held in holdingapparatus 820 is provided into the capillaries 812 under control of, forexample, compressed gas source 824. As the fluid composition 822 ispushed through the capillaries 812, a gas source 830, e.g., preferably acompressed gas source, provides compressed gas 830 around the dispensingtip 815 of capillary 812 and through opening 842 of each nozzlestructure 806. At least in part, the cone jet mode is provided at thedispensing end 810 of each of the nozzle structures by the compressedgas 830 flowing through opening 842 and around the capillary tube tip815 as further described below with reference to FIG. 8B.

FIG. 8B shows a more detailed diagram of each nozzle structure 806 ofthe air dispensing apparatus 800. As shown therein, the capillary tube812 includes a body portion 813 and the tip 815. Preferably, the tip 815is slightly tapered. The plate 840, which has the openings 842 definedtherein, includes a tapered region 839 defining each opening 842. Thetapered region 839 includes inner surfaces 841, i.e., inner relative tothe compressed gas 830, provides for receiving the compressed gas 830and applying aerodynamic force onto the meniscus of fluid composition822 formed at capillary tube tip 815. The cone jet 831 is formed therebywhich provides the spray of particles 808. It would be recognized thatthe tapered portion 839 may take one of various configurations. Forexample, such tapered surfaces 841 may include multiple tapers or may bearced, or further, may even include multiple tapered inner and outersurfaces as previously described herein with reference to FIGS. 5-6.

Further, other structures in addition to capillaries may be used toprovide the fluid composition in close proximity to the opening for 842.However, preferably, a capillary tube 812 having a tip 815 thereofpositioned below the upper surface 837 and in the opening 842 defined inthe plate 840 is employed.

Aerodynamic cone jets have been shown to produce particles having a sizeas small as 70 microns. For example, such cone jets are described in thearticle entitled “New Microfluidic Technologies to Generate RespirableAerosols for Medical Application,” by Afonso M. Ganan-Calvo, Journal ofAerosol Science, Vol. 30, Suppl. 1, pps. 541-542.

The dual structures, such as those shown in FIG. 6, may be implementedusing the aerodynamic structures shown in FIGS. 8A and 8B, as well. Forexample, multiple openings may be provided for each nozzle structure ina manner similar to that shown in FIGS. 8A and 8B. As such, for example,coated particles may be generated thereby.

As described herein, the present invention is particularly advantageousin coating medical devices such as stent structures (e.g., a stentstructure such as that shown generally and diagrammatically in FIG. 2).FIGS. 9A-9E show a holding fixture for use in coating such a stentstructure. Further, various embodiments of at least portions of coatingsystems are described with reference to FIGS. 10-16. Such systems areparticularly beneficial in coating stent structures but may also be usedin coating other medical devices such as those previously describedherein.

FIG. 9A shows a top view of a holding fixture 200 for holding a stent204 adjacent a dispensing apparatus 202 (e.g., a single or multiplecapillary tube electrospray apparatus). As shown in FIG. 9A, the stent204 is separated from the holding fixture 200 but would be placed on theholding fixture 200 in the region 203 when the coating method is beingperformed. The holding fixture 200 functions to not only hold the stentstructure 204, but also to ground the stent structure 204. FIG. 9B showsa side view of the holding fixture 200 with the stent structure 204apart from the apparatus 200.

The holding fixture 200 includes an elongated holding structure 206. Theholding structure 206 includes a pin holding spindle element 220 asfurther shown in greater detail in the detailed side view of FIG. 9C.The spindle element 220, e.g., a stainless steel spindle, includes abody member 205 that extends along axis 211 from a threaded first end223 to a second end 225. The threaded first end 223 of the spindleelement 220 is coupled to a corresponding threaded element 210 that isaffixed to a platform 201. All the elements of the holding fixture 200are mounted, either directly or indirectly, to the platform 201.

The spindle element 220 is moveably mounted by moveable holding elements208 (e.g., bearing structures) to allow for rotation of the spindleholding element 220. Rotation of the spindle element 220 is implementedby a coupling element 216 which couples the spindle element 220 to amotor 212. The motor 212 drives a shaft 217 that is connected via a beltor gear (not shown) to the spindle element 220 at notch 227 (see FIG.9C). As such, upon rotation of shaft 217, radial motion of spindleelement 220 is effected. The spindle element 220 rotates within theholding elements 208. Rotation is permitted by the rotation of threadedfirst end 223 within the threaded element 210 mounted to the platform201.

Further, the shaft 217 is moveable in a longitudinal direction alongaxis 250. Axis 250 lies substantially parallel to axis 211. Suchlongitudinal motion along axis 250 is translated through the couplingstructure 216 to the spindle element 220 effecting motion along axis211. The spindle element 220 is allowed to move in such a longitudinalmanner through openings of holding elements 208.

As such, and as would be recognized by one skilled in the art, thespindle element 220 can be rotated (i.e., radial motion about axis 211)as well as provided with movement along axis 211. The speed of suchrotation and longitudinal motion can also be controlled. One skilled inthe art will recognize that any type of structure providing suchlongitudinal and/or radial motion may be used according to the presentinvention and that the present invention is not limited to thisparticular structure.

As shown in further detail in FIGS. 9D and 9E, an elongated opening 243is defined at the second end 225 of the spindle element 220. The opening243 is sized for receiving a pin holding structure 230. The pin holdingstructure 230 is shown in further detail in FIG. 9D and generallyincludes a pin elongated body member 263 that extends from a first end241 along axis 211 (when mounted) to a second end 257. The pin elongatedbody member 263 is a conductive elongated body member (e.g., a tungstenpin member). The pin elongated body member 263 may be modified withnarrow circumferential rings of conductive or non-conductive material toprovide horizontal support for stents of increasing length. Further, thepin elongated body member 263 may also be made non-conductive, so thatthe stent itself is the only grounded feature in the spray path.

The elongated opening 243 of the spindle element 220 lies along axis 211and is configured to receive the first end 241 of the pin holdingstructure 230 and hold the pin holding structure 230 in the elongatedopening 243. A slot 245 is provided to accept a clip for holding the pinholding structure 230 within the elongated opening 243 at the second end225 of the spindle element 220.

Further, the pin holding structure 230 includes a tube element 261 sizedto be received over the pin elongated body member 263. The tube element261 (e.g., a nonconductive tube element) is also sized to allow thestent structure 204 to be positioned thereon. For example, in oneembodiment, the tube 261 is inserted over the pin elongated body member263 of the pin holding structure 230 and thereafter the pin elongatedbody member 263 and tube element 261 is inserted through the interiorvolume of the stent structure 204 such that the interior surface of thestent structure 204 is positioned adjacent to the tube element 261.

The pin holding structure 230 further includes a retaining structure 253at the second end 257 thereof. The retaining structure 253 includes atapered region 267 (e.g., an electrically conductive portion) forengaging and for use in grounding the stent as further described below.Generally, the retaining structure 253 need only be larger than thestent structure 204 to retain the stent structure on the pin holdingstructure 230 and include at least a conductive portion which can beused to ground the stent structure 204.

As described above, with the pin elongated boy member 263 and theelongated tube element 261 inserted into the stent structure 204, theinterior surface of stent structure 204 is adjacent the nonconductiveelongated tube 261. When the pin holding structure 230 is inserted intothe elongated opening 243 via end 241, the open end 269 (e.g., a taperedend) of the spindle element 220 contacts the nonconductive tube 261(e.g., Teflon elongated tube) and forces the tube element 261 toslightly expand such that the stent structure 204 is held stably inposition. In other words, the elongated tube element 261 is forced tocome in contact with the interior surface of the stent structure 204.

Further, likewise, at least a portion of the stent structure 204 isforced to come in contact with the tapered surfaces 267 of the retainingstructure 253. With the stent structure 204 in contact with theconductive material of the retaining structure 253, and the retainingstructure 253 in electrical contact with the conductive pin elongatedbody element 263, the stent structure 204 is easily grounded.

With the stent structure 204 in position, the dispensing apparatus 202may provide a plurality of particles for coating the stent structure204. During such coating process, the longitudinal and radial motion ofspindle element 220 can be provided for rotating and moving the stentstructure 204 radially and longitudinally. In one preferred embodiment,the timing of the rotation of the stent structure 204 about axis 211 andthe longitudinal movement of the stent structure 204 along axis 211 canbe controlled to coat the stent structure 204 in a single pass. Theconcentration of coating particles in the region 203 can also becontrolled to achieve such single pass coating. Likewise, one or morepasses may also be utilized to provide one or more coating layers and/orto provide a laminated type coating on the stent structure 204.

One skilled in the art will recognize that the holding fixture 200 isbut one exemplary embodiment of a holding fixture that can be used tolocate a stent structure at a particular position during a coatingprocess according to the present invention. Various other holdingstructures or components thereof are described herein. However, thepresent invention is not to be taken as being limited to any of thespecifically described configurations but only as described in theaccompanying claims.

FIG. 10A illustratively shows a perspective view of a stent coatingsystem 350 for coating one or more stent structures 340. FIG. 10B showsa cross-sectional view of a portion of the system 350. Generally, thecoating system 350 includes a body member 358, preferably a cylindricalbody member that extends along an axis 345 therethrough. Provided at theinterior of the cylindrical body member 358 are nozzle structures 362positioned radially about and also longitudinally along the axis 345.The nozzle structures 362 may be configured as capillary tubes, or maybe micro-machined openings such as described herein, or may include anyother type of nozzle structures suitable for providing particlesaccording to the present invention. The nozzle structures 362 arepreferably configured at the inner surface 359 of the body member 358.

In operation, the stent structures 340 are held within the body member358 with the axis 345 coinciding with an axis of the stent structures340. Any one of a number of different types of holding structures ortechniques may be used. Various holding structures and techniques aredescribed herein. However, the present invention is not limited to anyparticular holding structure but is only limited as described in theaccompanying claims. Generally, the stent structures 340, as previouslydescribed herein, include an open framework of stent material 341. Inother words, stent material 341 includes openings 342 between one ormore portions thereof.

With the stent structures 340 positioned within the body member 358, thestent structures 340 are grounded as shown by the illustrative groundingsymbol 373 in FIG. 10B. With the stent structures 340 grounded and ahigh voltage 353 applied to the nozzle structures 362, coating materialfrom a coating material source (e.g., a coating material reservoir 357)may be provided such that an electrospray of particles is establishedwithin the interior volume of the body member 358. With such particlesprovided, the electric field between the nozzle structures 362 and thestent structures 340 provide for the movement of the charged particlesto form a coating on the stent structures 340.

The spray of charged particles and the movement of such particlestowards the stent structure have been described previously herein. Assuch, further detail about the provision of the charged particles andthe movement thereof will not be further described.

One skilled in the art will readily ascertain from the previousdescription that the nozzle structures 362 and other nozzle structuresin the following embodiments may take the form of any one or more of thevarious different types of nozzle structure configurations describedherein. Further, such nozzle structures may be operated in any of themanners as described herein.

The reservoir for holding the coating material in the variousembodiments herein may take one of various different types ofconfigurations. For example, the reservoir may be a concentriccylindrical holding chamber for the source material as well as any otherdifferent type of configuration with operational elements for providinga feed of the source material to the one or more nozzle structures. Forexample, pressure may be applied to the source material, various gasstreams may be used to assist in providing such source material, etc.

FIGS. 11A and 11B show a perspective view and a cross-section view ofanother stent coating system 450 according to the present invention. Thecoating system 450 includes a body member 458, preferably a cylindricalbody member, extending along axis 445. The cylindrical body member 458includes longitudinal slots in the body member 458 that extend parallelto axis 445. The longitudinal slots are located in a radial manner aboutthe axis 445 to provide particles within the interior volume 459 of thecylindrical body member 458. A stent structure 440 is positioned withinthe body member 458 with its axis coincident with axis 445.

The stent structure 440 is held in place by an elongated element 446(e.g., a wire) with a plug at each end 475 to hold the stent structure440 in position. The longitudinal slots 470 are preferably equallyspaced about the body member 458. As such, each dispensing end of thelongitudinal slot 470 is generally of equidistance to the stentstructure 440.

FIG. 11B shows an illustrative cross-section view of FIG. 11A taken atline 11B-11B. The cross-section illustration shows a reservoir 457 forholding the coating material that is provided for the spray of particlesthrough the longitudinal slots 470 of the coating system 450. The stentstructure 440 is grounded, as shown schematically by ground 473, withthe nozzles being held at a high voltage 471 to establish the electricfield between the nozzle structures 470 and stent structure 440. Onewill recognize that there must be some protrusions at the longitudinalslot configuration 470, as previously discussed herein, in order toprovide a cone jet suitable for the spray of particles according to thepresent invention.

FIG. 12 shows yet another alternate portion of a medical device coatingsystem 650 which is substantially similar to that shown in FIGS. 11A and11B with a cylindrical body member 658 extending along axis 645.However, instead of longitudinal slots being used as part of the nozzlestructures as described with reference to FIGS. 11A and 11B, the stentcoating system 650 includes radially configured slots 670. The radialslots 670 are configured at a radial distance about axis 645. Aplurality of the radial slots 670 are positioned in a direction alongthe axis 645. With a stent structure 640 positioned such that its axisis coincident with the axis 645, the openings of the nozzle structuresformed by the radial slots 670 are equidistant from the stent structure640.

The radially configured slot configuration may include multiple arcsections of nozzle structures that substantially extend along the entirecircumference of the inner surface 659 of the body member 658 or,alternatively, such arc sections may only partially extend along aradial circumference of the inner surface 659. As shown in FIG. 12, twoarc sections are configured along the inner circumference on innersurface 659 of the body member 658.

FIGS. 13A-13C illustrate yet another exemplary portion of a stentstructure coating system 850 according to the present invention.Essentially, the body member 858 includes longitudinal slots 870 locatedparallel to axis 845 and spaced radially about the axis 845. Thisconfiguration is essentially the same as described with reference toFIGS. 11A and 11B. However, various embodiments of holding a stentstructure 840 to be coated located with its axis coincident with axis845 are shown in FIGS. 13A-13C.

With reference to 13A, one or more additional body members 880 may bepositioned along the axis 845 such that the stent structure 840 may becoated with one type of particles in the body member 858 and yet anothertype of particles in the body member 880. The body member 880 may beconfigured with nozzle structures (not shown) configured in any mannersuch as those described herein (e.g., the same or different nozzlestructures than used for body member 858).

Further, as shown in FIG. 13A, an elongated support element 857 is usedto assist in the coating process and hold the stent structure 840 inposition. As shown in FIG. 13B, the stent 840 is positioned with itsaxis coincident with axis 845 along which the elongated body member 858extends. Also extending along the axis 845 with its axis coincident withthe axis 845 of the stent structure 840 is an elongated support element857. The elongated support element 857 is positioned in the interior ofthe stent structure 840.

With the high voltage 853 applied to the nozzle structures 870 and thestent structure grounded (as shown schematically by ground 873), anelectric field 891 exists for moving the particles toward the stentstructure 840 as shown in FIG. 13C. Further, with an additional highvoltage 863 applied to elongated support wire 857 that is conductive, anadditional field 893 providing a force opposite to that of electricfield 891 is produced. As such, the stent structure 840 is held in aparticular position. Further, with proper adjustment of the fieldstrengths, it is possible to control the coating process such that theparticles to be coated on the stent structure 840 are substantiallymaintained on the outer surface of stent structure 840 to form a coating861 thereon.

As indicated above, this configuration of opposing fields provides notonly for the maintenance of the stent structure 840 in a stable positionalong the elongated support wire 857 but also operates to provide thecoating particles about the outer surface of the stent structure 840. Assuch, the interior surfaces thereof are maintained substantially free ofcoating material. In certain circumstances, a sheath may even beprovided over the stent structure. In other words, not only is the stentstructure material of the open framework of material coated with thecoating material, but the openings of the open framework material mayalso having coating material formed thereover to form the sheath.Additional sheath formation will further be described with reference toFIGS. 14A and 14B.

The forces generated by the opposing electric fields may also beprovided using other mechanical force techniques. For example, theelongated support element 857 may be a porous capillary that provides anair stream within the body member 858. The air stream provides the forceopposing that of the electrical field used to move the particles towardsthe stent structure 840. Further, the air stream may be used to maintainthe stent structure in a stable position.

Each of the above-mentioned techniques may be used to “levitate” thestent structure 840 from the support wire 857 while still maintaining itin a fixed position. Such levitation may provide for a more uniformcoating as other holding type fixtures may be eliminated. One skilled inthe art will recognize that the air suspension techniques described inU.S. Pat. No. 6,368,658 to Schwartz et al., entitled “Coating MedicalDevices Using Air Suspension,” issued Apr. 9, 2002, may also be used tohold the stent structure in place for coating according to the presentinvention.

FIGS. 14A and 14B further show a holding structure for holding a stentduring a coating process. As shown in FIG. 14A, an elongated element 935(e.g. a wire or tube) sized for contact with the inner surface of astent structure 940 is provided. The elongated element 935 preferably ismade of a nonconductive material such as Teflon. As such, with the stentstructure 940 grounded, coating particles will contact the stentmaterial 941 of the stent structure 940 to form a coating 938 thereover.The coating 938 may be formed not only on the stent material 941 but mayalso cover openings 942 in the open framework of stent material 941.After the coating 938 has been applied, the element 935 may be removed,leaving the coated stent structure as partially cut-away and shown inFIG. 14B.

In one embodiment of the elongated element 935, the element 935 may beexpanded to provide for stretching of the stent material when positionedwithin the interior volume of the stent structure 940 (e.g., the Teflontube as shown in the embodiment of FIG. 9). Thereafter, after thecoating 938 is applied on the stretched stent structure 948, the forceexpanding the elongated element 935 may be released and the element 935removed. The stent structure 940 may then collapse slightly.

Each of the methods of holding the stent structures in position alongthe axis of the coating system is constructed to prevent the stentstructure 940 from sagging. For example, if unsupported, the middle ofthe stent structure (i.e., the midpoint between a first and second endof the stent structure) may sag such that all the regions of the stentstructure are not equidistant from the axis extending therethrough. Withmany of the holding configurations described herein, such sagging iseliminated, or at least substantially reduced. Further, in one or morevarious embodiments of the present invention, if the stent structure iscoated in a vertical position, gravity may also prevent sagging.

Not only is the present invention advantageous for coating the outersurfaces of stent structures, inner surfaces defining interior volumesof stent structures may also be advantageously coated according to thepresent invention. As shown in FIG. 15, a coating system for coating aninterior surface 939 of a stent structure 940 that defines an interiorvolume thereof is illustrated.

Generally, the coating system shown in FIG. 15 is essentially the sameas that shown in FIGS. 11A and 11B for coating the outer surface of thestent structure 440. However, in addition, an elongated nozzle structure(e.g., a capillary tube 900) may be used to coat an interior surface 939of the stent structure 440. The stent structure 440 is grounded, asschematically shown by grounding element 473. With the high voltageapplied to the capillary tube 900, an electric field is establishedbetween the interior surface 939 of stent structure 440 and thecapillary tube 900 to form a cone jet and provide a spray of particles910 into the interior volume of the stent structure 440.

As shown in FIG. 15, the capillary tube 900 is preferably sized to beinsertable within the stent structure 440. Further, the capillary tube900 and/or the stent structure 440 can be moved along the axis 445 toprovide a uniform spray on the interior surface 939 thereof. AlthoughFIG. 15 illustrates a single nozzle structure in the form of a capillary900 providing a spray 910 of particles to coat the interior surface 939,one skilled in the art will recognize that an elongated structure havingmultiple nozzles yet sized to be received within the stent structure mayalso be used. Further, any nozzle configuration described herein mayalso be used to coat the interior surface 939.

Further, an element (e.g., a tube element) may be positioned about theouter surface of the stent structure to hold the stent structure 440 inplace during the interior surface coating process shown in FIG. 15. Assuch, just like the elongated element 935 as described with reference toFIGS. 14A-14B prevents coating on the interior surface, coating may beprevented from deposition on the exterior surface with use of such anelement. In such a manner, for example, an interior sheath may be formedon the interior surface.

In addition to moving the coating particles towards the stent structureusing an electric field, a thermophoretic effect may also be used tomove such particles towards a stent structure 940 as shown andillustrated in FIGS. 16A and 16B. As shown therein, thermophoreticforces are used to move particles 962 provided in the interior volume959 of a body member 958 toward the stent structure 940.

As used herein, the term thermophoretic force denotes the thermal forcethat is acting on a particle as a result of a temperature gradientassociated with the surrounding environment. The effect of thistemperature gradient on a given particle may be understood byconsidering the molecular forces impinging on the particle. Thosemolecules which strike the particle from a high temperature impart agreater impulse to the particle than those molecules which strike theparticle from the low temperature side. In addition, the practitionerskilled in the art will appreciate that concomitant radiation effectsmay augment these molecular forces. As a result of these and similareffects, the particle feels a net force directing it from the hottertemperature zone to the cooler temperature zone. This is thethermophoretic effect referred to herein.

As shown in FIG. 16A, the coating system 950 includes the body member958 that extends along axis 955 and is held at a higher temperature thanan elongated element 980 that extends through the stent structure 940(e.g., an element that may be or may not be in contact with the interiorsurface of the stent structure 940). The stent structure 940 is heldsuch that its axis is coincident with axis 955. As such, a temperaturegradient is established and the particles are moved towards the colderelongated element 980 as is shown in the cross-section view of FIG. 16B.With the particles moving towards the colder element 980, a coating 982is formed on the outer surface of the stent structure 940. The stentstructure 940 may be held within the body member 958 using any meanspreviously described herein or any other configuration which preferablyholds it at an equidistance from the heated portions of the body member958. In other words, the temperature gradient is preferably keptequivalent about the stent structure 940 in a radial fashion.

Preferably, as shown in FIGS. 16A and 16B, the elongated element 980 issized such that it is in contact with the inner surface of a stentstructure 940. In such a manner, an effective temperature gradient canbe established and particles are prohibited from depositing on the innersurface of the stent structure. In addition, as previously describedherein, with an elongated element contacting the inner surface of thestent structure, sagging of the stent structure can be reduced.

All patents, patent documents, and references cited herein areincorporated in their entirety as if each were incorporated separately.This invention has been described with reference to illustrativeembodiments and is not meant to be construed in a limiting sense. Asdescribed previously, one skilled in the art will recognize that othervarious illustrative applications may use the techniques as describedherein to take advantage of the beneficial characteristics of theparticles generated hereby. Various modifications of the illustrativeembodiments, as well as additional embodiments to the invention, will beapparent to persons skilled in the art upon reference to thisdescription.

1-61. (canceled)
 62. A system for use in coating at least one surface ofa medical device, the system comprising: a particle source; a holdingfixture operable to position a medical device in a defined volume; adispensing device configured to receive source material from theparticle source and dispense a plurality of monodisperse coatingparticles into the defined volume, wherein the dispensing devicecomprises one or more nozzle structures, wherein each nozzle structurecomprises at least one opening terminating at a dispensing end thereoffrom which a plurality of monodisperse coating particles having anelectrical charge applied thereto is dispensed; and an electrodestructure comprising an electrode isolated from the dispensing ends ofthe one or more nozzle structures, wherein the electrode structure isoperable to create a nonuniform electrical field between the dispensingends of the one or more nozzle structures and the medical device for usein providing the plurality of monodisperse coating particles in thedefined volume, wherein the plurality of monodisperse coating particleshave a nominal diameter of less than 10 micrometers and a geometricalstandard deviation of less than 1.2, and further wherein the nonuniformelectric field is operable to assist in moving a plurality of thecoating particles towards the at least one surface of the medical deviceto form a coating thereon.
 63. The system of claim 62, wherein theelectrode is a grounded medical device.
 64. The system of claim 62,wherein the electrode is a ring electrode positioned forward of one ormore of the nozzle structures.
 65. The system of claim 62, wherein thedispensing device is configured to dispense a spray of microdropletshaving an electrical charge associated therewith, wherein each of themicrodroplets comprises at least a particle, wherein the electricalcharge is concentrated on the particle as the microdroplet evaporates,and further wherein the electrical charge of the microdropletconcentrated on the particle is greater than about 30 percent of theRayleigh charge limit for the microdroplet.
 66. The system of claim 62,wherein the dispensing device is configured to dispense a spray ofmicrodroplets having an electrical charge associated therewith, whereineach of the microdroplets comprises at least a particle, wherein theelectrical charge is concentrated on the particle as the microdropletevaporates, and further wherein the position of the dispensing endsrelative to the medical device are such that, prior to contact with theat least one surface of the medical device, a residual particle volumeoccupied by the evaporated microdroplet comprises less than about 20percent of a solvent component of the microdroplet.
 67. The system ofclaim 62, wherein the medical device comprises a structure defining aninterior volume, wherein the structure comprises at least an interiorsurface adjacent the interior volume and at least an exterior surface,wherein the holding fixture is operable to position a medical devicesuch that at least one nozzle structure of the dispensing device isoperable within the interior volume defined by the structure.
 68. Thesystem of claim 67, wherein the electrode structure is operable tocreate a nonuniform electrical field between the dispensing end of theat least one nozzle structure and the medical device for use inproviding the plurality of monodisperse coating particles in theinterior volume of the medical device.
 69. The system of claim 67,wherein the at least one nozzle structure comprises an elongated elementsized to be positioned or moved into the defined interior volume of themedical device.
 70. The system of claim 62, wherein the dispensingdevice comprises a plurality of nozzle structures.
 71. The system ofclaim 62, wherein the holding fixture is configured to hold the medicaldevice in a fixed position within the defined volume.
 72. The system ofclaim 62, wherein the holding fixture is configured for movement of themedical device within the defined volume.
 73. The system of claim 62,wherein the holding fixture is configured to receive a stent structure,wherein the stent structure is defined along a stent axis, wherein thestent structure comprises at least an interior surface adjacent adefined interior volume and at least an exterior surface.
 74. The systemof claim 73, wherein the holding fixture is configured to at leastrotate the stent structure about the stent axis.
 75. The system of claim73, wherein the holding fixture is configured to at least move the stentstructure linearly along the stent axis.
 76. The system of claim 62,wherein the system further comprises a control system operable tocontrol the amount of monodisperse coating particles provided into thedefined volume.
 77. The system of claim 62, wherein the system furthercomprises a control system operable to adjust the strength of thenonuniform electrical field.
 78. The system of claim 62, wherein theparticle source comprises source material for use in providing aplurality of coating particles comprising at least one biologicallyactive ingredient or at least one coated biologically active ingredient.79. A system for use in coating at least one surface of a medicaldevice, the system comprising: particle generation apparatus operable toprovide a plurality of coating particles in a defined volume; a holdingfixture operable to position a stent structure defined along a stentaxis in the defined volume, wherein the stent structure comprises atleast an interior surface adjacent an interior volume and an exteriorsurface, wherein the holding fixture comprises an elongated elementlocated within the interior volume of the stent structure; and atemperature control apparatus operable to hold the elongated element ata lower temperature than the temperature in the defined volume adjacentthe exterior surface of the stent structure such that thermophoreticeffect moves the coating particles towards the at least one surface ofthe stent structure.
 80. A system for use in coating at least onesurface of a stent structure, the system comprising: a particle source;a holding fixture operable to position a stent structure defined along astent axis in a defined volume, wherein the stent structure comprises atleast an interior surface adjacent a defined interior volume and atleast an exterior surface; a dispensing device configured to receivesource material from the particle source and dispense a plurality ofmicrodroplets having an electrical charge associated therewith from thedispensing ends of the one or more nozzle structures into the definedvolume, wherein each of the microdroplets comprises at least a particle,and further wherein the electrical charge is concentrated on theparticles as the microdroplets evaporate resulting in a plurality ofcoating particles; and an electrode structure comprising an electrodeisolated from the dispensing ends of the one or more nozzle structures,wherein the electrode structure is operable to create a nonuniformelectrical field between the dispensing ends of the one or more nozzlestructures and the stent structure for use in providing the plurality ofcoating particles in the defined volume and moving the plurality ofcoating particles towards the stent structure to form a coating on theat least one surface thereof.
 81. The system of claim 80, wherein theelectrode is a grounded stent structure.
 82. The system of claim 80,wherein the electrode is a ring electrode positioned forward of one ormore of the nozzle structures.
 83. The system of claim 80, wherein theplurality of coating particles in the defined volume have a nominaldiameter of less than 10 micrometers and a geometrical standarddeviation of less than 1.2.
 84. The system of claim 80, wherein theplurality of microdroplets comprise a plurality of microdroplets thateach have electrical charge associated therewith that is greater thanabout 30 percent of the Rayleigh charge limit for the microdroplet. 85.The system of claim 80, wherein the position of the dispensing endsrelative to the stent structure is such that, prior to contact with theat least one surface of the stent structure, a residual particle volumeoccupied by the evaporated microdroplet comprises less than about 20percent of a solvent component of the microdroplet.
 86. The system ofclaim 80, wherein the holding fixture comprises: an elongatedsubstantially non-conductive tube for receiving the stent structurethereon; an elongated conductive element, wherein at least a portion ofthe elongated conductive element extends through the elongatedsubstantially non-conductive tube, and further wherein the elongatedconductive element comprises a conductive contact section; and acompression apparatus configured to provide for expansion of theelongated substantially non-conductive tube such that an exteriorsurface thereof is in contact with at least a portion of the interiorsurface of the stent structure and such that a portion of the stentstructure is in electrical contact with the conductive contact section.87. The system of claim 86, wherein the holding fixture is configured toat least rotate the stent structure about the stent axis.
 88. The systemof claim 86, wherein the holding fixture is configured to at least movethe stent structure linearly along the stent axis.
 89. The system ofclaim 80, wherein the holding fixture is configured to allow at leastone nozzle structure of the dispensing device to be operable within theinterior volume defined by the stent structure.
 90. The system of claim89, wherein the electrode structure is operable to create a nonuniformelectrical field between the dispensing end of the at least one nozzlestructure and the stent structure for use in providing the plurality ofcoating particles in the interior volume of the stent structure.
 91. Thesystem of claim 89, wherein the at least one nozzle structure comprisesa capillary tube comprised of a body portion and a tapered capillary tipat the dispensing end of the capillary tube.
 92. The system of claim 80,wherein the holding fixture is configured to hold the stent structure ina fixed position within the defined volume.
 93. The system of claim 80,wherein the holding fixture is configured for movement of the stentstructure within the defined volume.
 94. The system of claim 93, whereinthe holding fixture is configured to at least rotate the stent structureabout the stent axis.
 95. The system of claim 93, wherein the holdingfixture is configured to at least move the stent structure linearlyalong the stent axis.
 96. The system of claim 80, wherein the dispensingdevice comprises a plurality of nozzle structures.
 97. The system ofclaim 96, wherein the dispensing device comprises an elongatedcylindrical body member defining an interior volume thereof along anaxis, wherein the holding fixture is operable to position the stentstructure along the axis of the elongated cylindrical body member, andfurther wherein the one or more nozzle structures are positionedradially about the axis of the elongated cylindrical body member andlinearly along the elongated cylindrical body member in the direction ofthe axis thereof.
 98. The system of claim 97, wherein each of aplurality of the nozzle structures comprises a capillary tube comprisedof a body portion and a tapered capillary tip at the dispensing end ofthe capillary tube.
 99. The system of claim 97, wherein each of aplurality of the nozzle structures comprises a tapered portion used todefine an opening, and further wherein at least a part of each of theplurality of the nozzle structures extend from an integral conductiveportion associated with the body member.
 100. The system of claim 97,wherein each of a plurality of the nozzle structures comprises a solidpost along a center axis extending through an opening at the dispensingend.
 101. The system of claim 97, wherein each of a plurality of thenozzle structures comprises an elongated radial opening in the bodymember.
 102. The system of claim 97, wherein each of a plurality of thenozzle structures comprises an elongated opening in the body memberlying parallel to the axis thereof.
 103. The system of claim 80, whereinthe holding fixture comprises: an elongated element extending along anaxis, the axis of the stent structure coinciding with the axis of theelongated element when received thereon; and spacing elements operableto maintain a distance between the stent structure and the elongatedelement.
 104. The system of claim 80, wherein the holding fixturecomprises an elongated element, wherein the elongated element is sizedbased on the defined interior volume of the stent structure such that asurface of the elongated element is in direct contact with the interiorsurface of the stent structure.
 105. The system of claim 80, wherein theholding fixture comprises: a conductive elongated element along the axisof the stent structure, wherein the stent structure and the conductiveelongated element are spaced a distance apart; and a power sourceconfigured to create an electric field between the conductive elongatedelement and the stent structure that is opposite the nonuniform electricfield created between the dispensing ends of the nozzle structures andthe stent structure.
 106. The system of claim 80, wherein the holdingfixture comprises an elongated element along the axis of the stentstructure, wherein the stent structure and the elongated element arespaced a distance apart, the elongated element configured to provide agas stream within the defined interior volume of the stent structure.107. The system of claim 62, wherein at least one of the nozzlestructures comprises at least a first and second opening terminating atthe dispensing end of the nozzle structure.
 108. The system of claim107, wherein the particle source is configured to provide a first flowof a first fluid composition at the first opening and a second flow of asecond fluid composition at the second opening.
 109. The system of claim107, wherein the at least one surface of the medical device comprises aconductive surface.
 110. The system of claim 107, wherein the at leastone surface of the medical device comprises a non-conductive surface.111. The system of claim 107, wherein the at least one surface of themedical device comprises a polymer.
 112. The system of claim 107,wherein medical device comprises one or more exterior surfaces to becoated that define one or more openings to an interior thereof, andfurther wherein the medical device comprises one or more interiorsurfaces to be coated that lie in the interior defined by the one ormore exterior surfaces.
 113. The system of claim 107, wherein systemfurther comprises means for charging at least a portion of one or moresurfaces of the medical device.
 114. The system of claim 62, wherein thesystem further comprises masking material configured to be positionedproximate the medical device to prevent coating one or more portionsthereof.
 115. The system of claim 80, wherein at least one of the nozzlestructures comprises at least a first and second opening terminating atthe dispensing end of the nozzle structure.
 116. The system of claim115, wherein the particle source is configured to provide a first flowof a first fluid composition at the first opening and a second flow of asecond fluid composition at the second opening.
 117. The system of claim115, wherein the at least one surface of the medical device comprises aconductive surface.
 118. The system of claim 115, wherein the at leastone surface of the medical device comprises a non-conductive surface.119. The system of claim 115, wherein the at least one surface of themedical device comprises a polymer.
 120. The system of claim 115,wherein medical device comprises one or more exterior surfaces to becoated that define one or more openings to an interior thereof, andfurther wherein the medical device comprises one or more interiorsurfaces to be coated that lie in the interior defined by the one ormore exterior surfaces.
 121. The system of claim 115, wherein systemfurther comprises means for charging at least a portion of one or moresurfaces of the medical device.
 122. The system of claim 80, wherein thesystem further comprises masking material configured to be positionedproximate the medical device to prevent coating one or more portionsthereof.
 123. A system for use in coating at least one surface of amedical device, the system comprising: a particle source; a holdingfixture operable to position a medical device in a defined volume; adispensing device configured to receive source material from theparticle source and dispense a plurality of monodisperse coatingparticles into the defined volume, wherein the dispensing devicecomprises one or more nozzle structures, wherein each nozzle structurecomprises at least a first and second opening terminating at adispensing end thereof from which a plurality of monodisperse coatingparticles having an electrical charge applied thereto is dispensed; andan electrode structure comprising an electrode isolated from thedispensing ends of the one or more nozzle structures, wherein theelectrode structure is operable to create a nonuniform electrical fieldbetween the dispensing ends of the one or more nozzle structures and themedical device for use in providing the plurality of monodispersecoating particles in the defined volume, wherein the plurality ofmonodisperse coating particles have a nominal diameter of less than 10micrometers, and further wherein the nonuniform electric field isoperable to assist in moving a plurality of the coating particlestowards the at least one surface of the medical device to form a coatingthereon.
 124. The system of claim 123, wherein the particle source isconfigured to provide a first flow of a first fluid composition at thefirst opening and a second flow of a second fluid composition at thesecond opening.
 125. The system of claim 123, wherein the electrodecomprises a grounded medical device or a ring electrode positionedforward of one or more of the nozzle structures.
 126. The system ofclaim 123, wherein the dispensing device is configured to dispense aspray of microdroplets having an electrical charge associated therewith,wherein each of the microdroplets comprises at least a particle, whereinthe electrical charge is concentrated on the particle as themicrodroplet evaporates.
 127. The system of claim 123, wherein themedical device comprises a structure defining an interior volume,wherein the structure comprises at least an interior surface adjacentthe interior volume and at least an exterior surface, wherein theholding fixture is operable to position a medical device such that atleast one nozzle structure of the dispensing device is operable withinthe interior volume defined by the structure, wherein the electrodestructure is operable to create a nonuniform electrical field betweenthe dispensing end of the at least one nozzle structure and the medicaldevice for use in providing the plurality of monodisperse coatingparticles in the interior volume of the medical device.
 128. The systemof claim 123, wherein the medical device is a stent structure, andfurther wherein the holding fixture comprises: an elongatedsubstantially non-conductive tube for receiving the stent structurethereon; an elongated conductive element, wherein at least a portion ofthe elongated conductive element extends through the elongatedsubstantially non-conductive tube, and further wherein the elongatedconductive element comprises a conductive contact section; a compressionapparatus configured to provide for expansion of the elongatedsubstantially non-conductive tube such that an exterior surface thereofis in contact with at least a portion of the interior surface of thestent structure and such that a portion of the stent structure is inelectrical contact with the conductive contact section.
 129. The systemof claim 123, wherein the medical device is a stent structure, andfurther wherein the holding fixture is configured to rotate the stentstructure about the stent axis and/or move the stent structure linearlyalong the stent axis.
 130. The system of claim 123, wherein the medicaldevice is a stent structure, and further wherein the holding fixture isconfigured to allow at least one nozzle structure of the dispensingdevice to be operable within the interior volume defined by the stentstructure, wherein the electrode structure is operable to create anonuniform electrical field between the dispensing end of the at leastone nozzle structure and the stent structure for use in providing theplurality of coating particles in the interior volume of the stentstructure.
 131. The system of claim 123, wherein the medical device is astent structure, and further wherein the holding fixture comprises: anelongated element extending along an axis, the axis of the stentstructure coinciding with the axis of the elongated element whenreceived thereon; and spacing elements operable to maintain a distancebetween the stent structure and the elongated element.
 132. The systemof claim 123, wherein the medical device is a stent structure, andfurther wherein the holding fixture comprises an elongated element,wherein the elongated element is sized based on the defined interiorvolume of the stent structure such that a surface of the elongatedelement is in direct contact with the interior surface of the stentstructure.
 133. The system of claim 123, wherein the medical device is astent structure, and further wherein the holding fixture comprises: aconductive elongated element along the axis of the stent structure,wherein the stent structure and the conductive elongated element arespaced a distance apart; and a power source configured to create anelectric field between the conductive elongated element and the stentstructure that is opposite the nonuniform electric field created betweenthe dispensing ends of the nozzle structures and the stent structure.134. The system of claim 123, wherein the medical device is a stentstructure, and further wherein the holding fixture comprises anelongated element along the axis of the stent structure, wherein thestent structure and the elongated element are spaced a distance apart,the elongated element configured to provide a gas stream within thedefined interior volume of the stent structure.
 135. The system of claim123, wherein the system further comprises a control system operable toadjust the strength of the nonuniform electrical field.
 136. The systemof claim 123, wherein the particle source comprises source material foruse in providing a plurality of coating particles comprising at leastone biologically active ingredient or at least one coated biologicallyactive ingredient.
 137. The system of claim 123, wherein the pluralityof microdroplets comprise a plurality of microdroplets that each haveelectrical charge associated therewith that is greater than about 30percent of the Rayleigh charge limit for the microdroplet.
 138. Thesystem of claim 123, wherein the dispensing device is configured todispense a spray of microdroplets having an electrical charge associatedtherewith, wherein each of the microdroplets comprises at least aparticle, wherein the electrical charge is concentrated on the particleas the microdroplet evaporates, and further wherein the position of thedispensing ends relative to the medical device are such that, prior tocontact with the at least one surface of the medical device, a residualparticle volume occupied by the evaporated microdroplet comprises lessthan about 20 percent of a solvent component of the microdroplet. 139.The system of claim 123, wherein the at least one surface of the medicaldevice comprises a conductive surface.
 140. The system of claim 123,wherein the at least one surface of the medical device comprises anon-conductive surface.
 141. The system of claim 123, wherein the atleast one surface of the medical device comprises a polymer.
 142. Thesystem of claim 123, wherein medical device comprises one or moreexterior surfaces to be coated that define one or more openings to aninterior thereof, and further wherein the medical device comprises oneor more interior surfaces to be coated that lie in the interior definedby the one or more exterior surfaces.
 143. The system of claim 123,wherein system further comprises means for charging at least a portionof one or more surfaces of the medical device.
 144. The system of claim123, wherein the system further comprises masking material configured tobe positioned proximate the medical device to prevent coating one ormore portions thereof.